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Male Sprague (male + sprague)
Kinds of Male Sprague Terms modified by Male Sprague Selected AbstractsCocaine increases medial prefrontal cortical glutamate overflow in cocaine-sensitized rats: a time course studyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2004Jason M. Williams Abstract Excitatory amino acid transmission within mesocorticolimbic brain pathways is thought to play an important role in behavioural sensitization to psychomotor stimulants. The current studies evaluated a time course of the effects of cocaine on extracellular glutamate levels within the medial prefrontal cortex (mPFC) following increasing periods of withdrawal from repeated cocaine exposure. Male Sprague,Dawley rats underwent stereotaxic surgeries and were pretreated daily with saline (1 mL/kg/day × 4 days, i.p.) or cocaine (15 mg/kg/day × 4 days, i.p.) and withdrawn for 1, 7 or 30 days. After withdrawal rats were challenged with the same dose of saline or cocaine and in vivo microdialysis of the mPFC was conducted with concurrent analysis of locomotor activity. Animals that were withdrawn from repeated daily cocaine for 1 day and 7 days displayed an augmentation in cocaine-induced mPFC glutamate levels compared to saline and acute control subjects, which were similarly unaffected by cocaine challenge. At the 7 day time point, a subset of animals that received repeated cocaine did not express behavioural sensitization, nor did these animals exhibit the enhancement in mPFC glutamate in response to cocaine challenge. In contrast to these early effects, 30 days of withdrawal resulted in no significant changes in cocaine-induced mPFC glutamate levels regardless of the pretreatment or behavioural response. These data suggest that repeated cocaine administration transiently increases cocaine-induced glutamate levels in the mPFC during the first week of withdrawal, which may play an important role in the development of behavioural sensitization to cocaine. [source] Effects of sevoflurane on collagen production and growth factor expression in rats with an excision woundACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2010H.-J. LEE Background: Sevoflurane is a widely used inhalation anesthetic, but there are no studies on its effect on the wound-healing process. This study was undertaken to evaluate the effect of exposure time to sevoflurane on wound healing. Method: Male Sprague,Dawley rats were used. Two circular full-thickness skin defects 8 mm in diameter were made on the dorsum of the rats. The animals were divided into six groups according to exposed gas type and time: S1 (sevoflurane, 1 h), S4 (sevoflurane, 4 h), S8 (sevoflurane, 8 h), O1 (oxygen, 1 h), O4 (oxygen, 4 h), and O8 (oxygen, 8 h). The surface area of the wounds was measured 0, 1, 3, and 7 days after surgery. Separately, the mean blood pressures (MBP) and arterial oxygen pressures (PaO2) were monitored during the sevoflurane exposure. Collagen type I production and transforming growth factor-,1 (TGF-,1) and basic fibroblast growth factor (bFGF) expression on the wound surface were analyzed. Routine histological analysis was also performed. Result: Exposure duration to sevoflurane had no influence on MBP and PaO2. The reduction in wound size and collagen type I production was delayed in S8. The expression of TGF-,1 and bFGF on the wound surface in S8 was significantly attenuated in S8. The histology of the S8 demonstrated a delayed healing status. Conclusions: Prolonged exposure to sevoflurane might alter the inflammatory phase of the wound-healing process by attenuation of growth factor expression such as TGF-,1 and bFGF and subsequently by reduced collagen production. [source] Vitamin D and androgen regulation of prostatic growthJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2003Eddy S. Leman Abstract Vitamin D has been reported to inhibit the growth of prostate cancer cells and model systems. In this study, we examined the interaction between 1,25-dihydroxyvitamin D3 (1,25 D) in the presence or absence of endogenous testosterone on the growth and development of the adult rat prostate. Male Sprague,Dawley rats (165 days old) were either kept intact or castrated. Seven days after castration, the rats were treated with vehicle (control) or 1,25 D for 3 weeks and then sacrificed. Both ventral and dorsal lateral prostates were harvested; whole tissue lysates were collected and AR and VDR protein levels were analyzed by immunoblot analyses. Administration of 1,25 D in the intact animals decreased the prostatic size by 40%, compared to control animals, whereas 1,25 D did not influence the size of the prostate in castrated rats. 1,25 D administration in intact groups also increased both the AR and VDR protein levels by ,twofold, whereas in castrated groups, 1,25 D only increased the AR protein level by 1.5,2.5-fold. 1,25 D in the presence of endogenous testosterone inhibits prostatic growth, whereas 1,25 D in the absence of endogenous testosterone does not affect prostatic growth. The growth inhibitory activity of 1,25 D in the presence of testosterone may be mediated through the ligand activated AR and VDR pathways. These studies may reveal important information about the potential efficacy of 1,25 D as well as hormonal status in understanding the development of prostate diseases. J. Cell. Biochem. 90: 138,147, 2003. © 2003 Wiley-Liss, Inc. [source] A Soybean Cultivar Lacking Lipoxygenase 2 and 3 Has Similar Calcium Bioavailability to a Commercial Variety Despite Higher Calcium Absorption InhibitorsJOURNAL OF FOOD SCIENCE, Issue 3 2008H.S.D. Martino ABSTRACT:, The aim of this study was to evaluate calcium bioavailability of a new soybean variety without 2 lipoxygenases with better taste and flavor than a commercial variety containing all 3 isozymes. Using the femur 45Ca uptake method, calcium absorption from a new Brazilian variety, UFV-116, was compared to a common Brazilian variety, OCEPAR 19. Male Sprague,Dawley growing rats weighing 150 to 170 g (10/group) received test meals of whole fat soy flour prepared from UFV-116 or OCEPAR-19 seeds labeled with 10 ,Ci of 45Ca. Femurs were removed after 48 h for determination of 45Ca uptake. Calcium fractional absorption was equivalent between the 2 varieties. The higher oxalate:calcium molar ratio and the higher content of oxalate and phytate (P < 0.05) found in the UFV-116 variety did not affect calcium absorption. Therefore, the new variety is a comparable source of high bioavailable calcium. [source] Differential Effects of Restricted Versus Unlimited High-Fat Feeding in Rats on Fat Mass, Plasma Hormones and Brain Appetite RegulatorsJOURNAL OF NEUROENDOCRINOLOGY, Issue 7 2009T. Shiraev The rapid rise in obesity has been linked to altered food consumption patterns. There is increasing evidence that, in addition to total energy intake, the macronutrient composition of the diet may influence the development of obesity. The present study aimed to examine the impact of high dietary fat content, under both isocaloric and hypercaloric conditions, compared with a low fat diet, on adiposity, glucose and lipid metabolism, and brain appetite regulators in rats. Male Sprague,Dawley rats were exposed to one of three diets: control (14% fat), ad lib high-fat palatable (HFD, 35% fat) or high-fat palatable restricted (HFD-R, matched to the energy intake of control) and were killed in the fasting state 11 weeks later. Body weight was increased by 28% in unrestricted HFD fed rats, with an almost tripling of caloric intake and fat mass (P < 0.001) and double the plasma triglycerides of controls. Glucose intolerance and increased insulin levels were observed. HFD-R animals calorie matched to control had double their fat mass, plasma insulin and triglycerides (P < 0.05). Only ad lib consumption of the HFD increased the hypothalamic mRNA expression of the appetite-regulating peptides, neuropeptide Y and pro-opiomelanocortin. Although restricted consumption of palatable HFD had no significant impact on hypothalamic appetite regulators or body weight, it increased adiposity and circulating triglycerides, suggesting that the proportion of dietary fat, independent of caloric intake, affects fat deposition and the metabolic profile. [source] Role of Dopamine D1 Receptors and Extracellular Signal Regulated Kinase in the Motivational Properties of Acetaldehyde as Assessed by Place Preference ConditioningALCOHOLISM, Issue 4 2010Liliana Spina Background:, The role of dopamine D1 receptors and Extracellular signal Regulated Kinase (ERK) in the motivational properties of drugs can be studied by place-conditioning. Recent advances have shown that the motivational properties of ethanol, determined by place-conditioning, are mediated by its metabolic conversion into acetaldehyde. To date, the role of D1 receptors and ERK activation in acetaldehyde-elicited place preference has not been determined. The aim of this study was to assess the role of D1 receptors blockade and MEK inhibition in the acquisition of acetaldehyde-elicited conditioned place preference. Methods:, Male Sprague,Dawley rats were subjected to repeated pairings with 1 compartment of the conditioning apparatus immediately following acetaldehyde (20 mg/kg i.g.) or ethanol (1 g/kg i.g.) administration. The D1 receptor antagonist, SCH 39166 (50 ,g/kg s.c.), was administered 10 minutes before acetaldehyde or ethanol administration. In order to study the role of activated ERK in the acetaldehyde-elicited place preference, rats were administered the MEK inhibitor, PD98059 (1, 30, and 90 ,g i.c.v.), 10 or 30 minutes before acetaldehyde. To verify the specificity of these effects, we also studied whether PD98059 pretreatment could affect morphine (1 mg/kg s.c.)-elicited place preference. Results:, Both acetaldehyde and ethanol elicited significant place preferences and these were prevented by pretreatment with SCH 39166. In addition, pretreatment with PD98059, dose (30 and 90 but not 1 ,g i.c.v.) and time (10 but not 30 minutes before) dependently, prevented the acquisition of acetaldehyde- and significantly reduced the acquisition of morphine-elicited conditioned place preference. Conclusions:, These results confirm that acetaldehyde and ethanol elicit conditioned place preference and demonstrate that D1 receptors are critically involved in these effects. Furthermore, the finding that PD98059 prevents the acquisition of acetaldehyde-elicited conditioned place preference highlights the importance of the D1 receptor,ERK pathway in its motivational effects. [source] Chronic Alcohol Consumption Disrupted Cholesterol Homeostasis in Rats: Down-Regulation of Low-Density Lipoprotein Receptor and Enhancement of Cholesterol Biosynthesis Pathway in the LiverALCOHOLISM, Issue 3 2010Zhigang Wang Background:, Chronic alcohol consumption causes alcoholic liver disease, which is associated, or initiated, with dysregulated lipid metabolism. Very recent evidence suggested that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver diseases, however, the effects of chronic alcohol exposure on cholesterol homeostasis have not been well studied and underlying mechanisms behind are still elusive. Methods:, Male Sprague,Dawley rats weighing 250 ± 5.5 g (mean ± SEM) divided into 2 groups (8 rats per group) and pair-fed with liquid diets containing (in percent of energy intake) 18% protein, 35% fat, 12% carbohydrate, and 35% either ethanol (ethanol diet) or an isocaloric maltose-dextrin mixture (control diet), according to Lieber and De Carli, for 4 weeks. Results:, Long-term excessive alcohol feeding to rats caused fatty liver and liver injury, which was associated with disrupted cholesterol homeostasis, characterized by increased hepatic cholesterol levels and hypercholesterolemia. Hepatic cholesterol increases were concomitant with constantly activated sterol regulatory element-binding protein-2 (SREBP-2) in the liver and increased expression of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, a rate-limiting enzyme for cholesterol de novo synthesis, indicating enhanced cholesterol biosynthesis. Alcohol-induced hypercholesterolemia was accompanied by decreased LDL receptor (LDLr) levels in the liver. Further investigations revealed that chronic alcohol exposure increased hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) contents to down-regulate LDLr via a post-translational mechanism. Moreover, alcohol feeding suppressed extracellular signal-regulated kinase (ERK) activation in the liver. In vitro studies showed that inhibition of ERK activation was associated with decreased LDLr expression in HepG2 cells. Conclusions:, Our study provides the first evidence that both increased PCSK9 expression and suppressed ERK activation in the liver contributes to alcohol-induced hypercholesterolemia in rats. [source] Differential Central NOS-NO Signaling Underlies Clonidine Exacerbation of Ethanol-Evoked Behavioral ImpairmentALCOHOLISM, Issue 3 2010Tara S. Bender Background:, The molecular mechanisms that underlie clonidine exacerbation of behavioral impairment caused by ethanol are not fully known. We tested the hypothesis that nitric oxide synthase (NOS)-derived nitric oxide (NO) signaling in the locus coeruleus (LC) is implicated in this phenomenon. Methods:, Male Sprague,Dawley rats with intracisternal (i.c.) and jugular vein cannulae implanted 6 days earlier were tested for drug-induced behavioral impairment. The latter was assessed as the duration of loss of righting reflex (LORR) and rotorod performance every 15 minutes until the rat recovered to the baseline walk criterion (180 seconds). In a separate cohort, we measured p-neuronal NOS (nNOS), p-endothelial NOS (eNOS), and p-ERK1/2 in the LC following drug treatment, vehicle, or NOS inhibitor. Results:, Rats that received clonidine [60 Ig/kg, i.v. (intravenous)] followed by ethanol (1 or 1.5 g/kg, i.v.) exhibited synergistic impairment of rotorod performance. Intracisternal pretreatment with nonselective NOS inhibitor N, -nitro- l -arginine methyl ester (l -NAME, 0.5 mg) or selective nNOS inhibitor N -propyl- l -arginine (1 ,g) exacerbated the impairment of rotorod performance caused by clonidine,ethanol combination. Exacerbation of behavioral impairment was caused by l -NAME enhancement of the effect of ethanol, not clonidine. l -NAME did not influence blood ethanol levels; thus, the interaction was pharmacodynamic. LORR caused by clonidine (60 ,g/kg, i.v.),ethanol (1 g/kg, i.v.) combination was abolished by selective inhibition of central eNOS (l -NIO, 10 ,g i.c.) but not by nNOS inhibition under the same conditions. Western blot analyses complemented the pharmacological evidence by demonstrating that clonidine,ethanol combination inhibits phosphorylation (activation) of nNOS (p-nNOS) and increases the level of phosphorylated eNOS (p-eNOS) in the LC; the change in p-nNOS was paralleled by similar change in LC p-ERK1/2. NOS inhibitors alone did not affect the level of nitrate/nitrite, p-nNOS, p-eNOS, or p-ERK1/2 in the LC. Conclusions:, Alterations in NOS-derived NO in the LC underlie clonidine,ethanol induced behavioral impairment. A decrease in nNOS activity, due at least partly to a reduction in nNOS phosphorylation, mediates rotorod impairment, while enhanced eNOS activity contributes to LORR, elicited by clonidine,ethanol combination. [source] Effect of mivazerol, a ,2 -agonist, on striatal norepinephrine concentration during transient forebrain ischemia in rats,ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2008T. KIMURA Background: We have previously reported that mivazerol, a ,2 -agonist, possibly provides neuroprotection against transient forebrain ischemia in rats. This study was designed to investigate the ability of mivazerol to attenuate ischemia-induced increase in striatal norepinephrine concentration after transient forebrain ischemia in rats. Methods: Male Sprague,Dawley rats, anesthetized with halothane, were assigned to one of three groups (n=10 each); control (C, normal saline 1 ml/kg), mivazerol 20 ,g/kg (M20), and 40 ,g/kg (M40) groups. Monitored variables included temporal muscle temperature (maintained at 37.5±0.1 °C), electroencephalogram, systolic/diastolic blood pressure, heart rate, arterial blood gases, and blood glucose concentrations. Thirty minutes after subcutaneous drug administration, forebrain ischemia was induced with hemorrhagic hypotension (systolic arterial pressure: 40,50 mmHg) and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. Norepinephrine concentration in the interstitial fluids in the striatum was analyzed using in vivo microdialysis in combination with high-performance liquid chromatography. Results: Ischemia resulted in a prompt increase in norepinephrine concentrations in the striatum in all groups. However, there were no significant differences in norepinephrine concentrations in the striatum between the three groups at any period. Conclusions: Our results indicate that mivazerol did not attenuate ischemia-induced increase in striatal norepinephrine concentration. This suggests that the possible neuroprotective property of mivazerol is not related to inhibition of norepinephrine release in the brain. [source] Intestinal Dysbiosis: A Possible Mechanism of Alcohol-Induced Endotoxemia and Alcoholic Steatohepatitis in RatsALCOHOLISM, Issue 10 2009Ece Mutlu Background:, Clinical and animal data indicate that gut-derived endotoxin and other luminal bacterial products are necessary cofactors for development of alcoholic liver disease (ALD). Although gut leakiness is clearly an important cause of endotoxemia in ALD, it cannot fully explain endotoxemia in all ALD subjects and thus other factors may be involved. One possible factor is a change in gut microbiota composition (dysbiosis). Thus, the aim of our study was to interrogate the gut bacterial microbiota in alcohol-fed rats to see if chronic alcohol consumption affects gut bacteria composition. Method:, Male Sprague,Dawley rats were given either alcohol or dextrose intragastrically by gavage twice daily for up to 10 weeks. A subgroup of rats was also given either a probiotic (lactobacillus GG) or a prebiotic (oats) by gavage. Ileal and colonic mucosal-attached microbiota composition were interrogated by Length Heterogeneity PCR (LH-PCR) fingerprinting. Results:, Bacterial microbiota composition in alcohol-fed rats is not different from dextrose-fed rats at weeks 4 and 6. Mucosa-associated microbiota composition in the colon is altered at 10 weeks of daily alcohol gavage. Both LGG and oats prevented alcohol-induced dysbiosis up to 10 weeks of alcohol treatment. Conclusion:, Daily alcohol consumption for 10 weeks alters colonic mucosa-associated bacterial microbiota composition in rats. Our data showed, for the first time, that daily alcohol consumption can affect colonic microbiome composition and suggest that dysbiosis may be an important mechanism of alcohol-induced endotoxemia. Further studies are needed to determine how dysbiotic microbiota contributes to development of ALD and whether therapeutic interventions targeted towards dysbiotic microbiota can prevent complications of alcoholism like ALD. [source] Sirtinol attenuates hepatic injury and pro-inflammatory cytokine production following trauma-hemorrhage in male Sprague,Dawley ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2008F.-C. LIU Background: Although studies have demonstrated that sirtinol administration following adverse circulatory conditions is known to be protective, the mechanism by which sirtinol produces the salutary effects remains unknown. We hypothesized that sirtinol administration in male rats following trauma-hemorrhage decreases cytokine production and protects against hepatic injury. Methods: Male Sprague,Dawley rats underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min, then resuscitation). A single dose of sirtinol (1 mg/kg of body weight) or vehicle was administered intravenously during resuscitation. Twenty-four hours thereafter, tissue myeloperoxidase (MPO) activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 levels in the liver and plasma alanine aminotransferase (ALT) concentrations were measured (n=6 Sprague,Dawley rats/group). Results: Trauma-hemorrhage increased hepatic MPO activity, CINC-1, CINC-3, ICAM-1, and IL-6 levels and plasma ALT concentrations. These parameters were significantly improved in the sirtinol-treated rats subjected to trauma-hemorrhage. Conclusion: The salutary effects of sirtinol administration on attenuation of hepatic injury following trauma-hemorrhage are, at least in part, related to reduction of pro-inflammatory mediators. [source] Nitric Oxide-Mediated Intestinal Injury Is Required for Alcohol-Induced Gut Leakiness and Liver DamageALCOHOLISM, Issue 7 2009Yueming Tang Background:, Alcoholic liver disease (ALD) requires endotoxemia and is commonly associated with intestinal barrier leakiness. Using monolayers of intestinal epithelial cells as an in vitro barrier model, we showed that ethanol-induced intestinal barrier disruption is mediated by inducible nitric oxide synthase (iNOS) upregulation, nitric oxide (NO) overproduction, and oxidation/nitration of cytoskeletal proteins. We hypothesized that iNOS inhibitors [NG-nitro- l -arginine methyl ester (l -NAME), l -N6 -(1-iminoethyl)-lysine (l -NIL)] in vivo will inhibit the above cascade and liver injury in an animal model of alcoholic steatohepatitis (ASH). Methods:, Male Sprague,Dawley rats were gavaged daily with alcohol (6 g/kg/d) or dextrose for 10 weeks ± l -NAME, l -NIL, or vehicle. Systemic and intestinal NO levels were measured by nitrites and nitrates in urine and tissue samples, oxidative damage to the intestinal mucosa by protein carbonyl and nitrotyrosine, intestinal permeability by urinary sugar tests, and liver injury by histological inflammation scores, liver fat, and myeloperoxidase activity. Results:, Alcohol caused tissue oxidation, gut leakiness, endotoxemia, and ASH. l -NIL and l -NAME, but not the d -enantiomers, attenuated all steps in the alcohol-induced cascade including NO overproduction, oxidative tissue damage, gut leakiness, endotoxemia, hepatic inflammation, and liver injury. Conclusions:, The mechanism we reported for alcohol-induced intestinal barrier disruption in vitro , NO overproduction, oxidative tissue damage, leaky gut, endotoxemia, and liver injury , appears to be relevant in vivo in an animal model of alcohol-induced liver injury. That iNOS inhibitors attenuated all steps of this cascade suggests that prevention of this cascade in alcoholics will protect the liver against the injurious effects of chronic alcohol and that iNOS may be a useful target for prevention of ALD. [source] Ethanol Decreases Rat Hepatic Arylsulfatase A Activity LevelsALCOHOLISM, Issue 11 2006Smith Jean Background: Arylsulfatase A (ASA) is an enzyme that catalyzes the degradation of sulfatides, a glycosphingolipid found in many tissues, but predominantly in myelin and kidney. Arylsulfatase A is 1 member of a family of sulfatases that is activated by a required co- or posttranslational modification with the oxidation of cysteine to formylglycine. This conversion requires a novel oxygenase mechanism that can be inhibited by reactive oxygen species. Ethanol is known to cause an increase in reactive oxygen species in the liver. Because of its effect on the levels of hepatic reactive oxygen species, we hypothesized that ethanol would cause a specific decrease of rat hepatic ASA activity levels. Methods: Male Sprague,Dawley rats received ethanol-containing, Lieber,DeCarli liquid diets for 15 days, and control rats were pair-fed a liquid diet in which dextrose was isocalorically substituted for ethanol. Results: Arylsulfatase A activity levels decreased in livers of animals receiving alcohol compared with control animals. No significant changes in ASA activity levels were observed in the cerebral cortex and kidney. Furthermore, ethanol did not have any significant effect on hexosaminidase activity in any of the tissues examined. Conclusion: Ethanol caused a tissue-specific decrease in hepatic ASA activity levels, but not hexosaminidase activity levels. [source] Smoke Exposure and Ethanol Ingestion Modulate Intrapulmonary Polymorphonuclear Leukocyte Killing, but Not Recruitment or PhagocytosisALCOHOLISM, Issue 9 2006Elizabeth A. Vander Top Background: People who smoke and abuse alcohol are uniquely susceptible to pulmonary infections caused by Streptococcus pneumoniae, the pneumococcus. The primary cellular defense against pneumococci within the lungs is the polymorphonuclear leukocyte (PMN). Cigarette smoke and ethanol (EtOH) are known to alter certain PMN functions, but little is known about their concurrent effects. Methods: Male Sprague,Dawley rats were exposed twice daily for 8 weeks to cigarette smoke (smoke-exposed) or room air (sham-exposed). During the final week of exposure, the rats were pair-fed a liquid diet containing either 36 or 0% EtOH calories. Polymorphonuclear leukocytes were prerecruited into the rats' lungs by transtracheal injection of lipopolysaccharide. Five hours later, the rats were infected transtracheally with S. pneumoniae, and PMN recruitment, phagocytosis, and bactericidal activity were quantified within their lungs. Chemokine levels were also measured in bronchoalveolar lavage fluids, lung homogenates, and sera. Results: Neither PMN recruitment nor phagocytic uptake of pneumococci was altered by EtOH ingestion or smoke exposure. Killing of the organisms, however, was significantly decreased in sham-exposed, but not smoke-exposed, rats ingesting EtOH. Parallel results were determined for serum cytokine-induced neutrophil chemoattractant-1 (CINC-1), with EtOH ingestion significantly decreasing the levels in sham-exposed, but not smoke-exposed, rats. Pulmonary levels of macrophage inflammatory protein-2 (MIP-2) and CINC-1 were highly elevated by the combination of EtOH and smoke. Conclusions: One week of EtOH ingestion by rats impaired the ability of their PMNs to kill S. pneumoniae within their lungs. This was not due to decreased recruitment of the PMNs to the lungs or to diminished phagocytosis of intrapulmonary pneumococci. The addition of twice-daily cigarette smoke exposure to this short-term EtOH ingestion model restored PMN bactericidal ability to levels observed in the absence of either treatment. These EtOH-induced and smoke-induced alterations in PMN killing may be related to alterations in both pulmonary and systemic inflammatory chemokine levels. [source] A Microdialysis Profile of Dynorphin A1,8 Release in the Rat Nucleus Accumbens Following Alcohol AdministrationALCOHOLISM, Issue 6 2006Peter W. Marinelli Background: Pharmacological studies have implicated the endogenous opioid system in mediating alcohol intake. Other evidence has shown that alcohol administration can influence endorphinergic and enkephalinergic activity, while very few studies have examined its effect on dynorphinergic systems. The aim of the present study was to investigate the effect of alcohol administration or a mechanical stressor on extracellular levels of dynorphin A1,8 in the rat nucleus accumbens,a brain region that plays a significant role in the processes underlying reinforcement and stress. Methods: Male Sprague,Dawley rats were implanted with a microdialysis probe aimed at the shell region of the nucleus accumbens. Artificial cerebrospinal fluid was pumped at a rate of 1.5 ,L/min in awake and freely moving animals and the dialysate was collected at 30-minute intervals. In one experiment, following a baseline period, rats were injected intraperitoneally with either physiological saline or 1 of 3 doses of alcohol, 0.8, 1.6, or 3.2 g ethanol/kg body weight. In a second experiment, following a baseline period, rats were applied a clothespin to the base of their tail for 20 minutes. The levels of dynorphin A1,8 in the dialysate were analyzed with solid-phase radioimmunoassay. Results: Relative to saline-treated controls, an alcohol dose of 1.6 and 3.2 g/kg caused a transient increase in the extracellular levels of dynorphin A1,8 in the first 30 minutes of alcohol administration. However, the effect resulting from the high 3.2 g/kg dose was far more pronounced and more significant than with the moderate dose. There was no effect of tail pinch on dynorphin A1,8 levels in the nucleus accumbens. Conclusions: In this experiment, a very high dose of alcohol was especially capable of stimulating dynorphin A1,8 release in the nucleus accumbens. Dynorphin release in the accumbens has been previously associated with aversive stimuli and may thus reflect a system underlying the aversive properties of high-dose alcohol administration. However, the lack of effect of tail-pinch stress in the present study suggests that dynorphin A1,8 is not released in response to all forms of stressful/aversive stimuli. [source] Ethanol and red wine polyphenols induce the short-term downregulation of PAI-1 gene expression in vivo in rat aortic endotheliumJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2007Hernan E Grenett Abstract Moderate alcohol or red wine consumption reduces the risk of cardiovascular mortality. This cardiovascular protection is likely due to the additive, combined and/or synergistic effects of alcohol itself or other components of wine, in particular polyphenols. Experiments were carried out to determine whether ethanol/polyphenols also decrease plasminogen activator inhibitor type 1 (PAI-1) mRNA expression in vivo, using the rat as an animal model. Male Sprague,Dawley rats were gavaged with ethanol, the individual polyphenols catechin and quercetin or saline vehicle. The in vivo effect of ethanol or individual polyphenols on PAI-1 mRNA was then assessed by in situ hybridisation and quantitative reverse transcriptase (RT) polymerase chain reaction (RT-PCR). PAI-1 mRNA expression was significantly reduced in the endothelial and smooth muscle cells of the thoracic aorta of all experimental rats. RT-PCR analysis of PAI-1 mRNA levels in vascular tissue showed a ,55% reduction in PAI-1 mRNA consistent with the decrease in aortic endothelium PAI-1 mRNA observed with in situ hybridisation. This decrease may enhance endothelial cell (EC)-mediated fibrinolytic activity in vivo. The cardioprotection afforded by moderate red wine consumption can therefore be attributed in part to the combined effects of ethanol and individual polyphenols on EC fibrinolysis. Copyright © 2007 Society of Chemical Industry [source] Nerve growth factor and gastric hyperalgesia in the ratNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2003K. Lamb Abstract We recently demonstrated an association between the development of hyperalgesia and an increase in nerve growth factor (NGF) during gastric inflammation. We hypothesized that block of NGF signalling will blunt injury-induced hyperalgesia. Male Sprague,Dawley rats (300,400 g) were anaesthetized, the stomach was exposed and placed in a circular clamp. Acetic acid (60%) or saline (control) was injected into this area and aspirated 45 s later, resulting in kissing ulcers. A balloon was surgically placed into the stomach and electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. Animals received a daily injection of neutralizing NGF antibody or control serum for 5 days. NGF in the stomach wall was measured with an ELISA. The severity of gastric injury was assessed macroscopically and by determination of myeloperoxidase (MPO) activity. Gastric injury enhanced the visceromotor response to GD and increased NGF content. Anti-NGF significantly blunted the development of hyperalgesia and led to a decrease in gastric wall thickness and MPO activity. Increases in NGF contribute to the development of hyperalgesia after gastric injury. This may be partly mediated by direct effects on afferent nerves and indirectly by modulatory effects on the inflammatory response. [source] Right atrial stretch alters fore- and hind-brain expression of c-fos and inhibits the rapid onset of salt appetiteTHE JOURNAL OF PHYSIOLOGY, Issue 15 2008Juliana Irani Fratucci De Gobbi The inflation of an intravascular balloon positioned at the superior vena cava and right atrial junction (SVC-RAJ) reduces sodium or water intake induced by various experimental procedures (e.g. sodium depletion; hypovolaemia). In the present study we investigated if the stretch induced by a balloon at this site inhibits a rapid onset salt appetite, and if this procedure modifies the pattern of immunohistochemical labelling for Fos protein (Fos-ir) in the brain. Male Sprague,Dawley rats with SVC-RAJ balloons received a combined treatment of furosemide (Furo; 10 mg (kg bw),1) plus a low dose of the angiotensin-converting enzyme inhibitor captopril (Cap; 5 mg (kg bw),1). Balloon inflation greatly decreased the intake of 0.3 m NaCl for as long as the balloon was inflated. Balloon inflation over a 3 h period following Furo,Cap treatment decreased Fos-ir in the organum vasculosum of the lamina terminalis and the subfornical organ and increased Fos-ir in the lateral parabrachial nucleus and caudal ventrolateral medulla. The effect of balloon inflation was specific for sodium intake because it did not affect the drinking of diluted sweetened condensed milk. Balloon inflation and deflation also did not acutely change mean arterial pressure. These results suggest that activity in forebrain circumventricular organs and in hindbrain putative body fluid/cardiovascular regulatory regions is affected by loading low pressure mechanoreceptors at the SVC-RAJ, a manipulation that also attenuates salt appetite. [source] The Breakdown of Preformed Advanced Glycation End Products Reverses Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats: Preventive Versus Curative TreatmentTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2006Mustafa F. Usta MD ABSTRACT Objectives., Accumulation of advanced glycation end products (AGEs) has been linked to many of the complications of diabetes mellitus, including erectile dysfunction (ED). Furthermore, it has been demonstrated that inhibitors of AGE formation, such as aminoguanidine, can prevent ED in diabetic animals. However, it is unknown whether late administration of a putative cross-link breaker, ALT-711, can reverse diabetic ED. We therefore compared ALT-711 and aminoguanidine in their ability to reverse ED in diabetic rats. Materials and Methods., Male Sprague,Dawley rats were randomly divided into four groups: (i) age-matched controls; (ii) streptozotocin (STZ)-induced diabetic rats (60 mg/kg; intraperitoneal injection); (iii) STZ diabetic rats treated with ALT-711 (3 mg/kg/day, intraperitoneal injection); and (iv) STZ diabetic rats treated with aminoguanidine (1 gm/L in drinking water) during the final 6 weeks of 12 weeks of induced diabetes. At the end of 12 weeks, erectile response to cavernous nerve stimulation (CNS) was determined. Neuronal nitric oxide synthase (nNOS) contents were measured in all penises, and AGE levels were determined both in penile tissues and in serum samples. Results., Erectile responses to CNS and penile nNOS protein content were significantly reduced, while AGE levels were elevated in the penises and serum of untreated diabetic animals. Treatment with ALT-711, but not with aminoguanidine, reversed ED and nNOS depletion and reduced serum and penile tissue AGE levels. Conclusions., These results suggest that cross-link breakers, such as ALT-711, are the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in the reversal of diabetes-related ED. Usta MF, Kendirci M, Gur S, Foxwell NA, Bivalacqua TJ, Cellek S, and Hellstrom WJG. The breakdown of preformed advanced glycation end products reverses erectile dysfunction in streptozotocin-induced diabetic rats: Preventive versus curative treatment. J Sex Med 2006;3:242,252. [source] Effects of Ureaplasma urealyticum infection on the male reproductive system in experimental ratsANDROLOGIA, Issue 5 2010Y. Wang Summary To study the effects of Ureaplasma urealyticum (Uu) infection on the male reproductive system, the mechanism of infertility induced by Uu infection was investigated in experimental rats. Male Sprague,Dowley rats were infected with Uu4 (serotype 4) through repeated natural sexual intercourse for 8 weeks to establish infection. After 8 weeks, the blood samples of the animals were collected and analysed for cytokine production, and the animals were microdissected for the analysis of the reproductive system. Morphological study showed that spermatozoa exhibited curling and breaks in the rats infected at different dosages. Of the infected rats, 27.5% had both soft and hard calculi in the urinary tract, compared with 12% in the control groups. Uu infection resulted in a decline of sperm quality, eventually leading to the death of the spermatozoa. In the infected animals, the serum interleukin 6 and interleukin 8 levels increased significantly (P < 0.05), while tumour necrosis factor-alpha and interferon-gamma showed only modest changes. Our observations showed that Uu infection has an impact on sperm morphology, leading to the death of the spermatozoa. It is plausible that the morphological alterations of spermatozoa induced by Uu infection are one of the possible factors that contribute to male infertility. [source] Effect of sublingual medication of sildenafil citrate/ apomorphine on sexual behaviour of male ratsANDROLOGIA, Issue 2 2009X. Huang Summary The study investigated the combined effect of sublingually administered sildenafil (SN) and apomorphine (APO SL) on the sexual behaviour of male rats. Male Sprague,Dawley rats (50) were divided into five groups (10 rats per each group): blank control, sildenafil group and SN plus APO SL high dosage, medium dosage and low dosage group. After sublingual administration of the agents (control and SN plus APO SL) and a sole dosage of sildenafil (stomach irrigation), the rats were mated with female counterparts in pairs, and the latent period of chasing, the frequency of chasing in 60 min, the latent period of mounting and the frequency of mounting in 60 min were recorded. The lower dosage of SN plus APO SL exerted a stronger influence on the sexual activities in male rats than did the higher sole dosage of sildenafil. Identification of common neurochemical and neuroanatomical substrates of sexual responding between animals and humans suggests that the evolution of sexual behaviour has been highly conserved and indicates that animal models of human sexual response can be used successfully as pre-clinical tools. So sublingual medication of SN combined with APO SL may be at least a support inference about male sexual libido. [source] Effects of the combination of rapamycin with tacrolimus or cyclosporin on experimental intimal hyperplasiaBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2002Dr J. R. Waller Background: Allograft vasculopathy remains the leading cause of late allograft failure following transplantation and can be inhibited by the antiproliferative drug rapamycin. This study assessed the efficacy of combining rapamycin therapy with calcineurin inhibition. Methods: Male Sprague,Dawley rats received rapamycin 0·05 mg/kg daily and either tacrolimus 0·1 mg/kg or cyclosporin 5 mg/kg daily, and findings were compared with those in an untreated control group. Animals underwent left common carotid artery balloon angioplasty; the artery was explanted after 2 weeks. Morphometric analysis was performed on transverse sections and the intima: media ratio was calculated. Profibrotic gene expression was measured with competitive reverse transcriptase,polymerase chain reaction at 14 and 28 days. Proliferation was determined with proliferating cell nuclear antigen at 14 and 28 days. Extracellular matrix deposition was quantified with Sirius red. Results: The combination of rapamycin and tacrolimus was associated with the greatest reduction in intimal thickening. Furthermore, treatment with rapamycin and tacrolimus significantly attenuated extracellular matrix deposition compared with rapamycin and cyclosporin (P < 0·02). Conclusion: The effects of rapamycin in combination with tacrolimus were better than those observed with rapamycin and cyclosporin. © 2002 British Journal of Surgery Society Ltd [source] Reduction of vascular smooth muscle cell proliferation by immunomodulationBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2001Y. C. Chan Background: Immunological factors may play an important role in mediating the progression of atherosclerosis and myointimal hyperplasia, with heat shock proteins being implicated as possible autoantigens. The authors have shown previously that immunomodulation can reduce vascular smooth muscle cell (vSMC) proliferation following balloon injury to rat carotid arteries. The aim of the present study was to examine the effects of immunomodulatory agents on the proliferation of rat aortic vSMCs remote from the area of balloon injury. The agents used were SRL172 (heat-killed Mycobacterium vaccae) and heat shock protein 65 kDa (HSP65) in Freund's incomplete adjuvant. Both these agents are known to influence T-cell responses. Methods: Male Sprague,Dawley rats were used. All immunizations were given subcutaneously. Four groups were studied (ten animals in each group): group 1 animals were immunized with normal saline, group 2 received SRL172, group 3 SRL172 and HSP65,Freund's, and group 4 HSP65,Freund's. Three immunizations were performed as well as carotid balloon injury. Three animals died, leaving 37 for analysis. Some 5 weeks later the animals were killed and the aorta was harvested. Standard explant techniques were applied to grow aortic vSMCs until confluency, passaged three times, quiesced, and fetal calf serum (FCS) of varying concentrations (0·4,10 per cent) was then added, incubated for another 48 h and cell counts carried out. Results: The proliferation rate of aortic vSMCs in the control group was significantly greater than that in the other study groups (Fig.). While all the treatment groups had significantly less proliferation compared with the control group (*P < 0·05, ,P < 0·01, Mann,Whitney U test), no statistically significant differences existed between any of the study groups. Conclusion: Immunomodulation may result in a reduction of vSMC proliferation. Although the precise mechanisms involved are unclear, these results are in concordance with previous findings that T-cell immunomodulation decreases the development of myointimal hyperplasia after injury, and suggest that a fundamental phenotypic shift has been produced by these immunizations. [source] The effects of chronic administration of sumatriptan and dipyrone on serotonergic system in the rat brain: an immunohistochemical studyACTA NEUROLOGICA SCANDINAVICA, Issue 4 2009E. Genē Objective,,, To investigate the effects of chronic high dose sumatriptan and dipyrone treatment on central serotonergic system in rats. Materials and methods,,, Male Sprague,Dawley rats (seven per group) were daily injected with sumatriptan (3 mg/kg), dipyrone (400 mg/kg) or saline for 30 days. The brains of animals were surgically removed and immunohistochemically stained for serotonin. Serotonin-positive stained cells were counted automatically by using a computerized image analysis program. Statistical analysis carried out using one-way ANOVA followed by post hoc Tukey test. Results,,, A significant decrease in serotonin-positive cells in the brainstem was observed after chronic sumatriptan administration while chronic use of dipyrone induced a significant increase in serotonin-positive cells both in the cortex and midbrain. Conclusion,,, Our data suggest that central serotonergic system might be modified by chronic use of sumatriptan and dipyrone. [source] Downregulation of oxytocin receptors in right ventricle of rats with monocrotaline-induced pulmonary hypertensionACTA PHYSIOLOGICA, Issue 2 2010T. L. Broderick Abstract Aim:, Pulmonary hypertension (PH) in the rat leads to right ventricular (RV) hypertrophy, inflammation and increased natriuretic peptide (NP) levels in plasma and RV. Because the release of nitric oxide (NO) and atrial natriuretic peptide (ANP) is a function of the oxytocin receptor (OTR), we examined the effect of PH on gene and protein expression of OTR, NP (A, atrial; B, brain) and receptors (NPRs), nitric oxide synthases (NOS), interleukin (IL)-1,, IL-6 and tumour necrosis factor-, in the hypertrophied RV in a model of PH. Methods:, RV hypertrophy was induced in male Sprague,Dawley rats with monocrotaline (MCT; 60 mg kg,1) and was confirmed by the presence of an increased RV weight and RV-to-[left ventricle (LV) and septum] ratio. Results:, In the RV of MCT-treated rats, a ,40% reduction in OTR mRNA and protein was observed compared with the RV of control rats. This reduction was associated with increased transcripts of ANP and BNP in both ventricles and a corresponding increase in NP receptor mRNA expression for receptors A, B and C. Protein expression of inducible NOS was increased in the RV, whereas endothelial NOS transcripts were increased only in the LV of MCT-treated rats. In the RV of MCT-treated rats, downregulation of OTR was also associated with increased mRNA expression of IL-1, and IL-6. Conclusion:, Our results show that downregulation of the OTR in the RV of MCT-treated rats is associated with increased expression of NP and their receptors as well as IL-1, and IL-6. This reduction in OTR in RV myocardium may have an impact on cardiac function in the MCT-induced model of PH. [source] Exercise is the primary factor associated with Hsp70 induction in muscle of treadmill running ratsACTA PHYSIOLOGICA, Issue 4 2006E. G. Noble Abstract Aim:, The cytoprotective, inducible stress protein, Hsp70, increases in muscles of rodents subjected to strenuous treadmill running. Most treadmill running protocols employ negative reinforcement to encourage animals to exercise. As these stimuli may themselves activate stress responses, the present investigation was conducted to determine their contribution to the exercise-induced expression of Hsp70. Methods:, Twenty-one male Sprague,Dawley rats were randomly divided into three equal groups including an exercise group (EX), which ran on a treadmill at 30 m min,1 for 60 min; a stimulation group (STIM), which was not allowed to run, but was stimulated with compressed air and mild electric shock concurrently with their exercising cohort; and a control group (CON), which was housed in the treadmill room during the exercise period. Animals were killed 24 h post-experiment and hearts (H), soleii (SOL) and white gastrocnemii (WG) were harvested and analysed for Hsp70 content (mean% ± SEM of standard). Results:, Significant increases in Hsp70 (as a % of standard) were noted in H and WG (H = 77.4 ± 8.5; WG = 93.9 ± 18.4) of EX but not in STIM (H = 32.5 ± 4.6; WG = 32.0 ± 3.4) or CON (H = 20.5 ± 3.7; WG = 32.4 ± 7.4). In SOL, Hsp70 expression in EX (126.7 ± 6.2) was different from STIM (98.3 ± 10.9) only. This occurred, despite the fact that all groups were exposed to a stressful environment and exhibited elevated (P < 0.001) temperatures (EX ,41.2 ± 0.1 °C > STIM ,40.5 ± 0.2 °C > CON ,39.0 ± 0.1 °C) indicative of a general stress response. Conclusions:, These data suggest that exercise per se, rather than environmental conditions or noxious stimuli, are responsible for the induction of Hsp70 in rat muscle during treadmill running. [source] Effect of ,-trinositol on secretion induced by Escherichia coli ST-toxin in rat jejunumACTA PHYSIOLOGICA, Issue 4 2003A.-M. Lahti Abstract Aim:,d -myo-inositol-1,2,6-trisphosphate (, -trinositol, PP56), is a synthetic isomer of the intracellular second messenger, d -myo-inositol-1,4,5-trisphospahate. The pharmacological actions of , -trinositol include potent anti-inflammatory properties and inhibition of the secretion induced by cholera toxin and obstructive ileus. In the present study, we investigated whether , -trinositol was able to influence the secretion induced by heat-stable ST-toxin from Escherichia coli in the rat jejunum. Methods:, A midline abdominal incision was performed in anaesthetized male Sprague,Dawley rats and a 6,7 cm long jejunal segment was isolated with intact vascular supply and placed in a chamber suspended from a force displacement transducer connected to a Grass® polygraph. Intestinal net fluid transport was continuously monitored gravimetrically. Crystalline ST-toxin (120 mouse units) was introduced into the intestinal lumen and left there for the rest of the experiment. When a stable secretion was observed, , -trinositol (60 mg kg,1 h,1) or saline were infused during 2 h, followed by a 2-h control period. Results:, , -Trinositol induced a significant (P < 0.001) inhibition of ST-toxin secretion within 30 min, lasting until 2 h after infusion had stopped. The agent also moderately increased (P < 0.05) net fluid absorption in normal jejunum. Mean arterial pressure (P < 0.001) and heart rate (P < 0.001) were reduced by , -trinositol. Conclusion:, The inhibition by , -trinositol of ST-toxin induced intestinal secretion is primarily secondary to inhibition of secretory mechanisms and only to lesser extent due to increased absorption. The detailed mechanisms of action have not been clarified but may involve suppression of inflammation possibly by means of cellular signal transduction. [source] A Kindling Model of Pharmacoresistant Temporal Lobe Epilepsy in Sprague,Dawley Rats Induced by Coriaria Lactone and Its Possible MechanismEPILEPSIA, Issue 4 2003Ying Wang Summary: ,Purpose: The aim of this study was to develop a new animal model of pharmacoresistant temporal lobe epilepsy (TLE) by repeated intramuscular injection of Coriaria lactone (CL) at subthreshold dosages and to explore the mechanisms that might be involved. Methods: Healthy male Sprague,Dawley rats (n = 160) were randomized into four groups during the kindling process: three groups (n = 50 for each group) received CL injection at subthreshold dosages (1.25, 1.5, and 1.75 mg/kg, respectively), and ten received normal saline (NS) injection as a control group. The maximal human adult dosage of carbamazepine (CBZ), valproate (VPA), and phenytoin (PHT) was administered as monotherapy to different groups of kindled rats for 1 month (n = 20 for each group). Changes in EEG recording, seizure number, intensity (expressed as grade 1,5 according to Racine stage), and duration, including spontaneous seizures during different interventions, were compared. The expression of P-170, a multiple drug resistance gene (MDR1) encoding P-glycoprotein, was measured in brain samples from different groups of experimental rats by using an image analysis and measurement system (ImagePro-Plus 4.0). Results: A total of 70 (46.7%) rats were fully kindled with a median of 15 (seven to 20) CL injections. Electrocorticogram (ECoG) including hippocampal (EHG) monitoring revealed the temporal lobe origins of epileptiform potentials, which were consistent with the behavioral changes observed. Spontaneous seizures occurred with frequency and diurnal patterns similar to those of human TLE. The antiepileptic drugs (AEDs) tested lacked a satisfactory seizure control. The maximal P-170 expression was in the kindled rats with AED treatment; the next highest was in the kindled rats without AED intervention. Nonkindled SD rats with CL injection also had increased P-170 expression compared with control SD rats. Conclusions: The study provided a simple and stable animal TLE kindling model with pharmacoresistant properties. The pharmacoresistance observed in the kindled rats to CBZ, VPA, and PHT at maximal human adult dosages together with the increased P-170 expression was a distinct feature of this model. This model might be used in further investigations of the mechanisms involved in pharmacoresistant TLE and for developing new AEDs. [source] PRECLINICAL STUDY: Morphine withdrawal decreases responding reinforced by sucrose self-administration in progressive ratioADDICTION BIOLOGY, Issue 2 2007Dengke Zhang ABSTRACT Previous studies have shown that withdrawal from psychostimulant drugs such as d -amphetamine or methamphetamine decreases motivation to work for a natural reinforcement, which is thought to be associated with the withdrawal-induced depressive state and hypofunction of the mesolimbic dopamine system. However, to our knowledge, studies exploring the effect of morphine withdrawal on motivation for a natural reinforcement are lacking. The purpose of the present study was to examine whether motivation to work for a natural reinforcement changes during morphine withdrawal. Three groups of male Sprague,Dawley rats were trained to respond on a nose poke for a 4% sucrose solution under a progressive ratio schedule and were subsequently administered a 10-day regimen of injection of high or low dose of morphine or saline. Their duration of break point and withdrawal symptoms were assessed. The finding showed that break points were significantly reduced on day 1 and persisted to at least day 10 of withdrawal without change in locomotor activity. There were hardly any differences bear mentioning when comparing the magnitude of the decrease between the high- and the low-dose group, whereas the withdrawal scales were significant greater in the high-dose group than in the low-dose group. The results suggest that the morphine withdrawal resulted in decreased motivation to obtain the natural reinforcement. The progressive ratio procedure may be a useful technique for evaluation of changes in motivation for natural reinforcing stimuli following withdrawal from opiates. [source] Cannabinoid modulation of limbic forebrain noradrenergic circuitryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2010Ana F. Carvalho Abstract Both the endocannabinoid and noradrenergic systems have been implicated in neuropsychiatric disorders. Importantly, low levels of norepinephrine are seen in patients with depression, and antagonism of the cannabinoid receptor type 1 (CB1R) is able to induce depressive symptoms in rodents and humans. Whether the interaction between the two systems is important for the regulation of these behaviors is not known. In the present study, adult male Sprague,Dawley rats were acutely or chronically administered the CB1R synthetic agonist WIN 55,212-2, and ,2A and ,1 adrenergic receptors (AR) were quantified by Western blot. These AR have been shown to be altered in a number of psychiatric disorders and following antidepressant treatment. CB1R agonist treatment induced a differential decrease in ,2A- and ,1-ARs in the nucleus accumbens (Acb). Moreover, to assess long-lasting changes induced by CB1R activation, some of the chronically treated rats were killed 7 days following the last injection. This revealed a persistent effect on ,2A-AR levels. Furthermore, the localization of CB1R with respect to noradrenergic profiles was assessed in the Acb and in the nucleus of the solitary tract (NTS). Our results show a significant topographic distribution of CB1R and dopamine beta hydroxylase immunoreactivities (ir) in the Acb, with higher co-localization observed in the NTS. In the Acb, CB1R-ir was found in terminals forming either symmetric or asymmetric synapses. These results suggest that cannabinoids may modulate noradrenergic signaling in the Acb, directly by acting on noradrenergic neurons in the NTS or indirectly by modulating inhibitory and excitatory input in the Acb. [source] | |||||||||||||||||||||||||||||||