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Opioid System (opioid + system)
Kinds of Opioid System Selected AbstractsAmniotic fluid can act as an appetitive unconditioned stimulus in preweanling ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2007Carlos Arias Abstract Studies in humans and animals indicate that exposure to flavors in the amniotic fluid during the later gestational period may induce preferences for those flavors. Considering that during the last prenatal period the amniotic fluid contains substances that activate the opioid system, and that this system plays a critical role in the acquisition of olfactory preferences early in life, it has been hypothesized that the amniotic fluid may acquire appetitive unconditioned properties during this period. This has been tested in an experiment in which preweanling rats were exposed to alcohol odor (CS) paired or unpaired with the intraoral infusion of amniotic fluid (US) collected on gestational day 20. The pairing of these two stimuli induced an enhanced palatability of alcohol's flavor as well an increased intake of the drug. These results support the idea that amniotic fluid acquires appetitive unconditioned properties during the last days of gestation and suggest that associative mechanisms involving the amniotic fluid could be underlying odor and taste preferences acquired through fetal exposure. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 139,149, 2007. [source] PRECLINICAL STUDY: Modulation of MDMA-induced behavioral and transcriptional effects by the delta opioid antagonist naltrindole in miceADDICTION BIOLOGY, Issue 3 2009Emilie Belkaï ABSTRACT The delta opioid system is involved in the behavioral effects of various drugs of abuse. However, only a few studies have focused on the possible interactions between the opioid system and the effects of 3,4-methylenedioxymethamphetamine (MDMA). In order to examine the possible role of the delta opioid system in MDMA-induced behaviors in mice, locomotor activity and conditioned place preference (CPP) were investigated in the presence of naltrindole (NTI), a selective delta opioid antagonist. Moreover, the consequences of acute and chronic MDMA administration on pro-enkephalin (Penk) and pro-opiomelanocortin (Pomc) gene expression were assessed by real-time quantitative polymerase chain reaction (QPCR). The results showed that, after acute MDMA administration (9 mg/kg; i.p.), NTI (5 mg/kg, s.c.) was able to totally block MDMA-induced hyperlocomotion. Penk gene expression was not modulated by acute MDMA, but a decrease of Pomc gene expression was observed, which was not antagonized by NTI. Administration of the antagonist prevented the acquisition of MDMA-induced CPP, suggesting an implication of the delta opioid receptors in this behavior. Following chronic MDMA treatment, only the level of Pomc was modulated. The observed increase was totally blocked by NTI pre-treatment. All these results confirm the interactions between the delta opioid system (receptors and peptides) and the effects of MDMA. [source] PRECLINICAL STUDY: The effect of naltrexone on amphetamine-induced conditioned place preference and locomotor behaviour in the ratADDICTION BIOLOGY, Issue 3 2009Jenny Häggkvist ABSTRACT Whereas amphetamine and other psychostimulants primarily act on the dopamine system, there is also evidence that other neurotransmitter systems, such as the endogenous opioid system, modulate psychostimulant-induced effects. Several studies have investigated the role of opioid antagonists on cocaine-induced conditioned place preference (CPP), but there is limited information about the interaction with amphetamines. The aim of the present study was to investigate the effect of the opioid receptor antagonist, naltrexone (NTX) on the conditioning, expression and reinstatement of amphetamine-induced place preference. In addition, the effect of NTX on locomotor behaviour was measured during all sessions. During training, animals were conditioned with amphetamine (2 mg/kg) to induce place preference. In order to extinguish the conditioned behaviour, animals received saline for 12 days. Reinstatement of CPP was induced by a priming dose of amphetamine (0.5 mg/kg). The interaction of NTX and amphetamine was evaluated using three paradigms of CPP: with NTX (vehicle, 0.3, 1.0 and 3.0 mg/kg) administered either 30 minutes prior to amphetamine conditioning, or 30 minutes before the expression, or 30 minutes before the amphetamine priming to induce reinstatement. Naltrexone had no effect on the conditioning, the expression or the reinstatement induced by a priming dose of amphetamine. Further, NTX by itself did not induce place preference or place aversion. In contrast, NTX significantly attenuated the locomotor response to a priming dose of amphetamine without affecting general locomotor behaviour. The results suggest differences in opioid modulation of amphetamine-induced behaviours in the rat. [source] Opioids intrinsically inhibit the genesis of mouse cerebellar granule neuron precursors in vitro: differential impact of , and , receptor activation on proliferation and neurite elongationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Kurt F. Hauser Abstract Although opioids are known to affect neurogenesis in vivo, it is uncertain the extent to which opioids directly or indirectly affect the proliferation, differentiation or death of neuronal precursors. To address these questions, the intrinsic role of the opioid system in neurogenesis was systematically explored in cerebellar external granular layer (EGL) neuronal precursors isolated from postnatal mice and maintained in vitro. Isolated neuronal precursors expressed proenkephalin-derived peptides, as well as specific , and ,, but negligible ,, opioid receptors. The developmental effects of opioids were highly selective. Morphine-induced , receptor activation inhibited DNA synthesis, while a preferential ,2 -receptor agonist ([d -Ala2]-deltorphin II) or Met-enkephalin, but not the ,1 agonist [d -Pen2, d -Pen5]-enkephalin, inhibited differentiation within the same neuronal population. If similar patterns occur in the developing cerebellum, spatiotemporal differences in endogenous , and , opioid ligand,receptor interactions may coordinate distinct aspects of granule neuron maturation. The data additionally suggest that perinatal exposure to opiate drugs of abuse directly interfere with cerebellar maturation by disrupting normal opioid signalling and inhibiting the proliferation of granule neuron precursors. [source] Opioids and the skin , where do we stand?EXPERIMENTAL DERMATOLOGY, Issue 5 2009Paul L. Bigliardi Abstract:, The common ectodermal origin of the skin and nervous systems can be expected to predict likely interactions in the adult. Over the last couple of decades much progress has been made to elucidate the nature of these interactions, which provide multidirectional controls between the centrally located brain and the peripherally located skin and immune system. The opioid system is an excellent example of such an interaction and there is growing evidence that opioid receptors (OR) and their endogenous opioid agonists are functional in different skin structures, including peripheral nerve fibres, keratinocytes, melanocytes, hair follicles and immune cells. Greater knowledge of these skin-associated opioid interactions will be important for the treatment of chronic and acute pain and pruritus. Topical treatment of the skin with opioid ligands is particularly attractive as they are active with few side effects, especially if they cannot cross the blood,brain barrier. Moreover, cutaneous activation of the opioid system (e.g. by peripheral nerves, cutaneous and immune cells, especially in inflamed and damaged skin) can influence cell differentiation and apoptosis, and thus may be important for the repair of damaged skin. While many of the pieces of this intriguing puzzle remain to be found, we attempt in this review to weave a thread around available data to discuss how the peripheral opioid system may impact on different key players in skin physiology and pathology. [source] Hypericum caprifoliatum (Guttiferae) Cham.FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2006& Schltdl.: a species native to South Brazil with antidepressant-like activity Abstract In this work, previously published and unpublished results on biological activity of Hypericum caprifoliatum, a native specie to South Brazil, are presented. Lipophilic extracts obtained from this species showed an antidepressant-like activity in mice and rat forced swimming test. Results from in vivo experiments suggest an effect on the dopaminergic transmission. Besides that, in vitro experiments demonstrated that the extract and its main component (a phloroglucinol derivative) inhibit monoamine uptake in a concentration-dependent manner, more potently to dopamine, but this effect is not related to direct binding at the uptake sites. It was also observed that a 3-day treatment with lipophilic extract prevents stress-induced corticosterone rise in mice frontal cortex but not in plasma. The lipophilic and methanolic H. caprifoliatum extracts also demonstrated antinociceptive effect, which seems to be indirectly mediated by the opioid system. These results indicate that H. caprifoliatum presents a promising antidepressant-like effect in rodents which seems to be related to a mechanism different from that of other classes of antidepressants. [source] Alcohol potentiates hepatitis C virus replicon expressionHEPATOLOGY, Issue 1 2003Ting Zhang Alcohol consumption accelerates liver damage and diminishes the anti-hepatitis C virus (HCV) effect of interferon alfa (IFN-,) in patients with HCV infection. It is unknown, however, whether alcohol enhances HCV replication and promotes HCV disease progression. The availability of the HCV replicon containing hepatic cells has provided a unique opportunity to investigate the interaction between alcohol and HCV replicon expression. We determined whether alcohol enhances HCV RNA expression in the replicon containing hepatic cells. Alcohol, in a concentration-dependent fashion, significantly increased HCV replicon expression. Alcohol also compromised the anti-HCV effect of IFN-,. Investigation of the mechanism(s) responsible for the alcohol action on HCV replicon indicated that alcohol activated nuclear factor ,B (NF-,B) promoter. Caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-,B, abolished alcohol-induced HCV RNA expression. In addition, naltrexone, an opiate receptor antagonist, abrogated the enhancing effect of alcohol on HCV replicon expression. In conclusion, alcohol, probably through the activation of NF-,B and the endogenous opioid system, enhances HCV replicon expression and compromises the anti-HCV effect of IFN-,. Thus, alcohol may play an important role in vivo as a cofactor in HCV disease progression and compromise IFN-,-based therapy against HCV infection. [source] Opioid receptor antagonist promotes angiogenesis in bile duct ligated ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2009Negar Faramarzi Abstract Background and Aim:, Angiogenesis, formation of new capillaries from existing vasculature, plays a pivotal role in different pathological states such as many chronic inflammatory diseases including the chronic liver diseases. There is increasing evidence demonstrating accumulation of endogenous opioids and their role in the pathophysiology and manifestations of cholestasis, the main feature of a number of chronic progressive liver diseases. Hence, we investigated the significance of endogenous opioids in angiogenesis in an experimental model of cholestasis. Methods:, Cholestasis was induced in male Sprague,Dawley rats by bile duct ligation and resection. Naltrexone, an opioid antagonist (20 mg/kg/day) was administered to cholestatic animals for 22 ± 1 days. The serial sections from liver tissue were stained with von Willebrand Factor antibody and micro-vessel density was assessed by calculating mean micro-vessel number in three hot spots high power microscopic fields. Results:, Naltrexone treatment in bile duct ligated rats led to a marked increase in the micro-vessel number (6.34 ± 0.21 vs 5.61 ± 0.22) (P < 0.05), which had already increased during cholestasis. Conclusion:, In order to clarify the impacts of opioid system blockade in cirrhosis, our findings demonstrate the promoting role of opioid antagonist in angiogenesis in a rat model of cholestasis. [source] Opioidergic regulation of astroglial/neuronal proliferation: where are we now?JOURNAL OF NEUROCHEMISTRY, Issue 4 2008Tim J. Sargeant Abstract Opiate drugs, such as codeine, morphine, and heroin, are powerful analgesics, but also are used as drugs of abuse because of their psychogenic properties. Many studies have shown that opiates impact on cellular proliferation in the adult and developing brain, although anatomical pathologies are lacking in in utero exposed infants and opioid knockout mice. Recent research has defined a context-dependent role for the opioid system in neurogenesis in the adult hippocampus with exercise. Opioids have been shown to interact with proliferating cells of the postnatal subventricular zone of the lateral ventricles. The subventricular zone is also a region of adult neurogenesis, a fact that was not well established at the time this earlier research was conducted. Although a relationship between opioids and fetal neurogenesis has yet to be firmly established, many studies have implicated the opioid system in this process. One common factor that links neurogenesis in adult, postnatal, and fetal structures is the involvement of neuronal progenitor cells of the astrocytic lineage. It is therefore of interest that opioids have been consistently shown to impact upon astrocytic proliferation. It is the intention of this paper to review the literature that has established a role for the opioid system in neurogenesis in vivo in fetal, postnatal, and adult animals and to examine the links of opioids to modulation of astrocytic proliferation. [source] ,-Opioid receptor knockout mice are insensitive to methamphetamine-induced behavioral sensitizationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 10 2010Xine Shen Abstract Repeated administration of psychostimulants to rodents can lead to behavioral sensitization. Previous studies, using nonspecific opioid receptor (OR) antagonists, revealed that ORs were involved in modulation of behavioral sensitization to methamphetamine (METH). However, the contribution of OR subtypes remains unclear. In the present study, using ,-OR knockout mice, we examined the role of ,-OR in the development of METH sensitization. Mice received daily intraperitoneal injection of drug or saline for 7 consecutive days to initiate sensitization. To express sensitization, animals received one injection of drug (the same as for initiation) or saline on day 11. Animal locomotor activity and stereotypy were monitored during the periods of initiation and expression of sensitization. Also, the concentrations of METH and its active metabolite amphetamine in the blood were measured after single and repeated administrations of METH. METH promoted significant locomotor hyperactivity at low doses and stereotyped behaviors at relative high doses (2.5 mg/kg and above). Repeated administration of METH led to the initiation and expression of behavioral sensitization in wild-type mice. METH-induced behavioral responses were attenuated in the ,-OR knockout mice. Haloperidol (a dopamine receptor antagonist) showed a more potent effect in counteracting METH-induced stereotypy in the ,-OR knockout mice. Saline did not induce behavioral sensitization in either genotype. No significant difference was observed in disposition of METH and amphetamine between the two genotypes. Our study indicated that the ,-opioid system is involved in modulating the development of behavioral sensitization to METH. © 2010 Wiley-Liss, Inc. [source] Region-Specific Induction of FosB/,FosB by Voluntary Alcohol Intake: Effects of NaltrexoneALCOHOLISM, Issue 10 2010Jing Li Background:, ,FosB is the best characterized transcription factor induced by chronic stimulation. Although previous studies have demonstrated that chronic passive ethanol exposure alters ,FosB immunoreactivity (IR), the effect of chronic voluntary ethanol consumption on ,FosB remains unknown. Furthermore, although previous studies have demonstrated that the opioid antagonist naltrexone reduces alcohol consumption in clinical and preclinical settings, the effect of naltrexone on FosB/,FosB has not been explored. Here, we examined the effects of chronic voluntary ethanol intake and naltrexone on FosB/,FosB IR in striatal region and prefrontal cortex, and the effect of naltrexone on voluntary ethanol intake. Methods:, We utilized immunohistochemistry to define the changes in FosB/,FosB IR induced by chronic voluntary ethanol intake under a two-bottle intermittent access of 20% ethanol model and by systematic administration (intraperitoneal injection) of naltrexone in Sprague-Dawley rats. Results:, Chronic (15 drinking sessions in 35 days) voluntary ethanol intake robustly induces FosB/,FosB IR in nucleus accumbens core, dorsolateral striatum, and orbitofrontal cortex, but not in nucleus accumbens shell, dorsomedial striatum, and medial prefrontal cortex. Systemic administration of naltrexone for 6 days significantly reduced voluntary ethanol consumption and FosB/,FosB IR induced by chronic voluntary ethanol intake. Conclusion:, Our results suggest that chronic voluntary ethanol intake induces FosB/,FosB IR in a subregion-specific manner which involves the activation of endogenous opioid system. [source] Dexamethasone reduces morphine-induced straub reaction in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2002Anna Capasso This study examined the effect of dexamethasone on morphine-induced straub reaction in mice. When morphine was administered in doses of 7.5, 15 and 30 mg kg,1 intraperitoneally, a dose-dependent straub reaction was produced. Dexamethasone per-se (0.1,10 mg kg,1 i.p.) did not modify the tail of control mice. Pre-treatmentwith dexamethasone 120 min before morphine injection caused a dose-dependent reduction of straub reaction. Cycloheximide (1 5 mg kg,1 i.p.) administered 2 h before morphine did not change morphine-induced straub reaction, but was able to prevent the effects of dexamethasone on morphine-induced straub reaction. The glucocorticoid receptor antagonist RU-38486 (15 mg kg,1 i.p.) did not affect morphine-induced straub reaction, whereas it was able to block the effects of dexamethasone on morphine-induced straub reaction. Results of this study indicate that dexamethasone reduced morphine-mediated straub reaction in mice, indicating a further important functional interaction between dexamethasone and the opioid system. The ability of cycloheximide and RU-38486 to block dexamethasone's effects indicates that the steroid's interference with morphine-mediated straub reaction involves a protein-synthesis-dependent mechanism via gluco-corticoid receptors. [source] Opioids in the Hypothalamic Paraventricular Nucleus Stimulate Ethanol IntakeALCOHOLISM, Issue 2 2010Jessica R. Barson Background:, Specialized hypothalamic systems that increase food intake might also increase ethanol intake. To test this possibility, morphine and receptor-specific opioid agonists were microinjected in the paraventricular nucleus (PVN) of rats that had learned to drink ethanol. To cross-validate the results, naloxone methiodide (m-naloxone), an opioid antagonist, was microinjected with the expectation that it would have the opposite effect of morphine and the specific opioid agonists. Methods:, Sprague,Dawley rats were trained, without sugar, to drink 4 or 7% ethanol and were then implanted with chronic brain cannulas aimed at the PVN. After recovery, those drinking 7% ethanol, with food and water available, were injected with 2 doses each of morphine or m-naloxone. To test for receptor specificity, 2 doses each of the ,-receptor agonist [d -Ala2,N -Me-Phe4,Gly5 -ol]-Enkephalin (DAMGO), ,-receptor agonist d -Ala-Gly-Phe-Met-NH2 (DALA), or ,-receptor agonist U-50,488H were injected. DAMGO was also tested in rats drinking 4% ethanol without food or water available. As an anatomical control for drug reflux, injections were made 2 mm dorsal to the PVN. Results:, A main result was a significant increase in ethanol intake induced by PVN injection of morphine. The opposite effect was produced by m-naloxone. The effects of morphine and m-naloxone were exclusively on intake of ethanol, even though food and water were freely available. In the analysis with specific receptor agonists, PVN injection of the ,-agonist DALA significantly increased 7% ethanol intake without affecting food or water intake. This is in contrast to the ,-agonist U-50,488H, which decreased ethanol intake, and the ,-agonist DAMGO, which had no effect on ethanol intake in the presence or absence of food and water. In the anatomical control location 2 mm dorsal to the PVN, no drug caused any significant changes in ethanol, food, or water intake, providing evidence that the active site was close to the cannula tip. Conclusions:, The ,-opioid receptor agonist in the PVN increased ethanol intake in strong preference over food and water, while the ,-opioid agonist suppressed ethanol intake. Prior studies show that learning to drink ethanol stimulates PVN expression and production of the peptides enkephalin and dynorphin, which are endogenous agonists for the ,- and ,-receptors, respectively. These results suggest that enkephalin via the ,-opioid system can function locally within a positive feedback circuit to cause ethanol intake to escalate and ultimately contribute to the abuse of ethanol. This is in contrast to dynorphin via the ,-opioid system, which may act to counter this escalation. Naltrexone therapy for alcoholism may act, in part, by blocking the enkephalin-triggered positive feedback cycle. [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] A Polymorphism of the ,-Opioid Receptor Gene (OPRM1) and Sensitivity to the Effects of Alcohol in HumansALCOHOLISM, Issue 12 2004Lara A. Ray Background: Recent research has implicated the endogenous opioid system in the development of alcohol use disorders. The A118G polymorphism of the OPRM1 gene has been shown to confer functional differences to ,-opioid receptors, such that the G variant binds ,-endorphin three times more strongly than the A variant. The goal of this study was to test whether the A118G polymorphism is associated with sensitivity to the effects of alcohol. Methods: Participants who were either homozygous for the A allele (n= 23) or heterozygous (n= 15) received intravenous doses of alcohol designed to reach three target levels of breath alcohol concentration: 0.02, 0.04, and 0.06. The testing procedure consisted of measures of subjective intoxication, stimulation, sedation, and mood states at baseline and at each of the three target breath alcohol concentrations. Results: The results suggested that individuals with the G allele reported higher subjective feelings of intoxication, stimulation, sedation, and happiness across trials as compared with participants with the A allele. Furthermore, participants with the G allele were almost three times more likely to report a positive family history of alcohol use disorders than participants with the A allele. Conclusions: These findings may help to explain previous research suggesting that naltrexone is more effective among individuals with the G allele. A medication that reduces feelings of euphoria after alcohol consumption may be more successful among individuals with a genetic predisposition to greater feelings of euphoria after consuming alcohol. [source] Serum 6-Beta-Naltrexol Levels Are Related to Alcohol Responses in Heavy DrinkersALCOHOLISM, Issue 9 2000Mary E. McCaul Background: There is strong evidence for the role of the endogenous opioid system in alcohol reinforcement and consumption; however, recent human laboratory studies and clinical trials have reported mixed effects of naltrexone (a nonselective opioid antagonist) on alcohol-related behaviors. This paper reports a secondary data analysis of a human laboratory study that examines the relationship between serum levels of 6-beta-naltrexol, the major, biologically active metabolite of naltrexone, and subjective effects of alcohol. Methods: The study used a within-subjects design to examine the effects of naltrexone (0, 50, and 100 mg/day) on subjective responses to alcohol (none, moderate, and high dose) in heavy drinkers (n= 23). Each subject received three doses of naltrexone in random order; each naltrexone dose was administered over an 8 day period on an inpatient unit, with a 1 week outpatient washout between doses. After stabilization at each of the naltrexone doses, subjects participated in three alcohol challenge sessions (none, moderate, and high dose) in random order; thus, each subject participated in a total of nine alcohol administration sessions. Results: Doubling the naltrexone dose (50 vs. 100 mg/day) doubled the mean serum 6-beta-naltrexol levels. At each naltrexone dose, there was a 4-fold range in 6-beta-naltrexol levels across subjects. Before alcohol administration, higher 6-beta-naltrexol levels were associated with higher ratings of sedation. After high-dose alcohol administration, higher 6-beta-naltrexol levels were associated with significantly lower ratings of liking and best effects. Conclusions: These findings provide further evidence of the involvement of the opioid system in the modulation of alcohol effects and suggest that serum 6-beta-naltrexol concentrations may be important in predicting therapeutic response to naltrexone. [source] Involvement of ,-opioid receptors in visceral nociception in miceNEUROGASTROENTEROLOGY & MOTILITY, Issue 10 2008M. H. Larsson Abstract, It has been shown that the behavioural responses to chemically evoked visceral nociception are increased in transgenic mice lacking the ,-opioid receptor (KOR). The aim of the present study was to evaluate the contribution of KOR in mechanically evoked visceral pain by performing colorectal distension (CRD) and monitoring the subsequent visceromotor response (VMR) in control mice (KOR+/+) and in mice lacking KOR (KOR,/,). Pseudo-affective visceral pain responses were evoked in conscious mice using increasing (10,80 mmHg) and repeated (12,×,55,mmHg) phasic CRD paradigms. The resulting VMR was determined by monitoring the electromyographic activity of the abdominal muscle. The increasing and repeated CRD paradigms, respectively, evoked similar responses in both KOR+/+ and KOR,/, mice. The selective KOR-agonists U-69593 (5 and 25 mg kg,1, s.c.) and asimadoline (25 mg kg,1, s.c.) significantly decreased the VMR in KOR+/+ mice, while having no effect in KOR,/, mice. In contrast, the selective ,-opioid receptor agonist fentanyl significantly reduced the VMR in both types of mice and appeared more efficacious in KOR,/, mice. The opioid receptor antagonist naloxone (0.3,30 mg kg,1 s.c.) did not affect the response to CRD in C57BL/6 mice at any dose tested. In conclusion, the data confirm that the KOR agonists used in this study inhibit the VMR to CRD in mice by acting via KOR receptors. In addition, the data suggest that the endogenous opioid system is not likely to modulate the VMR to mechanically evoked visceral pain in mice. [source] Effect of crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in micePHYTOTHERAPY RESEARCH, Issue 5 2010Hossein Hosseinzadeh Abstract Crocus sativus L. has been shown to interact with the opioid system. Thus, the effects of aqueous and ethanolic extracts of stigma and its constituents were evaluated on morphine-withdrawal syndrome in mice. Dependence was induced using subcutaneous (s.c.) injections of morphine for 3 days. On day 4, morphine was injected 0.5,h prior the interaperitoneal (i.p.) injections of the extracts, crocin, safranal, clonidine (0.3,mg/kg) or normal saline. Naloxone was injected (5,mg/kg i.p.) 2,h after the final dose of morphine and the number of episodes of jumping during 30,mm was considered as the intensity of the withdrawal syndrome. Clonidine, the aqueous and ethanolic extracts of saffron reduced the jumping activity. Safranal was injected (s.c.) 30,mm prior and 1 and 2,h after the injection of morphine. It potentiated some signs of withdrawal syndrome. The aqueous extract decreased the movement in all of the doses (80, 160, 320,mg/kg) and the ethanolic extract decreased it in the dose of 800,mg/kg in open field test. But crocin and the dose of 400,mg/kg ethanolic extract showed no effect on activity in this test. It is concluded that the extracts and crocin may have interaction with the opioid system to reduce withdrawal syndrome. Copyright © 2009 John Wiley & Sons, Ltd. [source] Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline in rat locus coeruleus neuronsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2003Eduardo Ruiz-Durántez The aim of this study was to determine if 2-(2-benzofuranyl)-2-imidazoline (2-BFI) interacts with the opioid system in the rat locus coeruleus, using single-unit extracellular recordings. In morphine-dependent rats, acute administration of the selective imidazoline receptor ligands 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) or valldemossine (10 mg kg,1, i.p.) did not modify the naloxone-induced hyperactivity of locus coeruleus neurons compared with that observed in the morphine-dependent control group. After chronic administration of 2-BFI (10 mg kg,1, i.p., three times daily, for 5 days) and morphine, naloxone-induced hyperactivity and tolerance to morphine were attenuated. This effect was not observed when a lower dose of 2-BFI (1 mg kg,1, i.p.) or valldemossine (10 mg kg,1, i.p.) were used. Acute administration of 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) but not valldemossine (40 mg kg,1, i.p.) diminished the potency of morphine to inhibit locus coeruleus neuron activity in vivo (ED50 values increased by 2.3, 2.9; and 3.1 fold respectively). Similarly, the potency of Met5 -enkephalin to inhibit locus coeruleus neurons was decreased when 2-BFI (100 ,M) was applied to rat brain slices (EC50 increased by 5.6; P<0.05). The present data demonstrate that there is an interaction between 2-BFI and the opioid system in the locus coeruleus. This interaction leads to an attenuation of both the hyperactivity of locus coeruleus neurons during opiate withdrawal and the development of tolerance to morphine when 2-BFI is chronically administered. These results suggest that imidazoline drugs may prove to be useful agents for the management of opioid dependence and tolerance. British Journal of Pharmacology (2003) 138, 494,500. doi:10.1038/sj.bjp.0705052 [source] Classical conditioning in the rat fetus: Involvement of mu and kappa opioid systems in the conditioned responseDEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2002William P. Smotherman Abstract When the Embryonic Day 20 (E20) rat fetus is given a conditioning trial involving a paired presentation of an artificial nipple (the conditioned stimulus; CS) with an intraoral infusion of milk (the unconditioned stimulus; US), it shows evidence of classical conditioning when again exposed to the CS during a test trial. Specifically, the fetus shows fewer oral grasp responses (the conditioned response; CR) when continuously presented with the artificial nipple. The present study further investigated this classically conditioned reduction in oral grasping. Separate experiments (a) examined the time course of the reduction in oral grasping (Experiment 1), (b) characterized the time course of mu opioid (Experiment 2) and kappa opioid (Experiment 3) involvement in the CR, and (c) described changes in fetal behavior (Experiment 4) associated with mu and kappa opioid effects on responding to the artificial nipple. The results are discussed in terms of opioid involvement in establishing and maintaining early suckling behavior. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 104,115, 2002. DOI 10.1002/dev.10016 [source] Ethanol-Induced Social Facilitation in Adolescent Rats: Role of Endogenous Activity at Mu Opioid ReceptorsALCOHOLISM, Issue 6 2009Elena I. Varlinskaya Background:, Ethanol consumption is considerably elevated during adolescence. Attractiveness of alcohol for humans during the adolescent developmental period is based, in part, on its ability to induce social facilitation,a facilitation of social interactions not only evident in human adolescents but also in adolescent rats. Endogenous opioid systems are among the multiple neural systems implicated in the behavioral and reinforcing effects of ethanol and may play a substantial role in modulating stimulatory effects of low doses of ethanol on social behavior during adolescence. This possibility was explored in the present study through the use of an animal model of peer-directed social behavior. Methods:, Sprague,Dawley rats were challenged early in adolescence with saline or ethanol intraperitoneally (i.p.), placed into an individual holding cage for 30 minutes, and then tested in a familiar situation with a nonmanipulated partner of the same age and sex. In Experiment 1, each test subject was injected subcutaneously with one of the three doses of a nonselective opioid antagonist naloxone (0, 0.05, and 0.1 mg/kg), 5 minutes prior to the social interaction test and 25 minutes following challenge with saline or ethanol (0.5 g/kg), whereas in Experiment 2 animals were challenged with one of the six doses of ethanol (0, 0.25, 0.5, 0.75, 1.0, and 1.25 g/kg) prior to injection of either saline or naloxone (0.05 mg/kg). In Experiment 3, animals were pretreated i.p. with the selective ,-opioid antagonist CTOP (0, 0.01, 0.025, 0.05, and 0.1 mg/kg) 30 minutes prior to challenge with saline or ethanol (0.5 g/kg). Results:, Low doses of ethanol (0.5 and 0.75 g/kg) produced social facilitation, as indexed by significant increases in play fighting and social investigation. Both doses of naloxone and the three highest doses of CTOP blocked the stimulatory effects of ethanol on play fighting but not on social investigation. These effects were not associated with alterations in ethanol pharmacokinetic properties or with shifts in the biphasic ethanol dose,response curve. Conclusions:, Ethanol-induced facilitation of social play behavior seen in adolescent animals is mediated in part through ethanol-induced release of endogenous ligands for the ,-opioid receptor or an ethanol-associated enhancement of sensitivity of these receptors for their endogenous ligands. [source] Effects of CRF1 -Receptor and Opioid-Receptor Antagonists on Dependence-Induced Increases in Alcohol Drinking by Alcohol-Preferring (P) RatsALCOHOLISM, Issue 9 2008Nicholas W. Gilpin Background:, Selective breeding of rats over generations and induction of alcohol dependence via chronic vapor inhalation both enhance alcohol consumption in animal models. The purpose of this study was to determine whether dependence-induced increases in alcohol consumption by P rats is sensitive to naltrexone, a general opioid receptor antagonist (but with highest affinity at the ,-opioid receptor at low doses), and the recently characterized small molecule CRF1 -receptor antagonist MPZP (N,N -bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5- a]pyrimidin-7-amine). Methods:, P rats (n = 20) were trained to respond for alcohol and water in a 2-lever operant situation during daily 30-minute sessions. P rats were then matched for alcohol intake and exposed to chronic intermittent alcohol vapor (n = 10) or ambient air (n = 10) for approximately 10 weeks. All rats were then administered MPZP and naltrexone in 2 separate and consecutive Latin-square designs. Results:, MPZP attenuated dependence-induced increases in alcohol intake by P rats while having no effect on alcohol consumption by nondependent controls. Conversely, operant alcohol responding was reduced similarly in dependent and nondependent P rats by naltrexone. Conclusions:, These results confirm a role for brain CRF1 -receptor systems in dependence-induced changes in the reinforcing properties of alcohol, and CRF1 -receptor blockade appears to suppress dependence-induced drinking at lower doses in P rats relative to other rat lines. Therefore, brain CRF1 -receptor systems are important in the regulation of dependence-induced alcohol consumption, whereas brain opioid systems are important in the regulation of basal alcohol consumption by rats. [source] The endocannabinoid system in brain reward processesBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008M Solinas Food, drugs and brain stimulation can serve as strong rewarding stimuli and are all believed to activate common brain circuits that evolved in mammals to favour fitness and survival. For decades, endogenous dopaminergic and opioid systems have been considered the most important systems in mediating brain reward processes. Recent evidence suggests that the endogenous cannabinoid (endocannabinoid) system also has an important role in signalling of rewarding events. First, CB1 receptors are found in brain areas involved in reward processes, such as the dopaminergic mesolimbic system. Second, activation of CB1 receptors by plant-derived, synthetic or endogenous CB1 receptor agonists stimulates dopaminergic neurotransmission, produces rewarding effects and increases rewarding effects of abused drugs and food. Third, pharmacological or genetic blockade of CB1 receptors prevents activation of dopaminergic neurotransmission by several addictive drugs and reduces rewarding effects of food and these drugs. Fourth, brain levels of the endocannabinoids anandamide and 2-arachidonoylglycerol are altered by activation of reward processes. However, the intrinsic activity of the endocannabinoid system does not appear to play a facilitatory role in brain stimulation reward and some evidence suggests it may even oppose it. The influence of the endocannabinoid system on brain reward processes may depend on the degree of activation of the different brain areas involved and might represent a mechanism for fine-tuning dopaminergic activity. Although involvement of the various components of the endocannabinoid system may differ depending on the type of rewarding event investigated, this system appears to play a major role in modulating reward processes. British Journal of Pharmacology (2008) 154, 369,383; doi:10.1038/bjp.2008.130; published online 14 April 2008 [source] | |||||||||||||||||||||||||