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Terms modified by I.c.v. Selected AbstractsThe effects of intracerebroventricular AM-251, a CB1-receptor antagonist, and ACEA, a CB1-receptor agonist, on penicillin-induced epileptiform activity in ratsEPILEPSIA, Issue 7 2009Ramazan Kozan Summary Purpose:, Several results support the conclusion that the cannabinoid system has a role in generation and cessation of epileptic seizures. The aim of this study was to evaluate the effects of intracerebroventricular AM-251 [N -(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], a CB1-receptor antagonist, and ACEA (arachidonyl-2-chloroethylamide), a CB1-receptor agonist, on penicillin-induced epileptiform activity in rats. Methods:, In the first set of experiments, 30 min after penicillin injection, AM-251, at doses of 0.125, 0.25, 0.5, and 1 ,g, was administered intracerebroventricularly (i.c.v.). In the second set of experiments, 30 min after penicillin injection, ACEA, at doses of 2.5, 5, 7.5, and 15 ,g (i.c.v.), was administered. In the third set of experiments, AM-251, at doses of 0.125 and 0.25 ,g (i.c.v.), was administered 10 min before ACEA (7.5 ,g, i.c.v.) injection. Results:, ACEA, at a dose of 7.5 ,g, significantly decreased the frequency of penicillin-induced epileptiform activity without changing the amplitude. ACEA, at doses of 2.5, 5, and 15 ,g, had no impact on either frequency or amplitude of epileptiform activity. AM-251, at doses of 0.25 and 0.50 ,g, significantly increased the frequency of epileptiform activity. AM-251, at a dose of 0.25 ,g (i.c.v.), was the most effective in changing the frequency of penicillin-induced epileptiform activity, and it also caused status epilepticus,like activity. AM-251, at doses of 0.125 and 0.25 ,g, 10 min before ACEA (7.5 ,g), reversed the anticonvulsant action of ACEA. Discussion:, The results of the present study provide electrophysiologic evidence for the role of CB1 receptors in regulating the frequency of epileptiform activity in the model of penicillin-induced epilepsy. To elucidate the precise mechanism of cannabinoid action in the brain during seizure, more advanced electrophysiologic and neurochemical studies are required. [source] Neuropeptide Y suppresses absence seizures in a genetic rat model primarily through effects on Y2 receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Margaret J. Morris Abstract Neuropeptide Y (NPY) potently suppresses absence seizures in a model of genetic generalized epilepsy, genetic absence epilepsy rats of Strasbourg (GAERS). Here we investigated the Y-receptor subtype(s) on which NPY exerts this anti-absence effect. A dual in vivo approach was used: the cumulative duration of seizures was quantified in adult male GAERS in 90-min electroencephalogram recordings following intracerebroventricular (i.c.v.) injection of: (i) subtype-selective agonists of Y1 ([Leu31Pro34]NPY, 2.5 nmol), Y2 (Ac[Leu28,31]NPY24,36, 3 nmol), Y5 receptors [hPP1,17,Ala31,Aib32]NPY, 4 nmol), NPY (3 nmol) or vehicle; and following (ii) i.c.v. injection of antagonists of Y1 (BIBP3226, 20 nmol), Y2 (BIIE0246, 20 nmol) and Y5 (NPY5RA972, 20 nmol) receptors or vehicle, followed by NPY (3 nmol). Injection of the Y1 - and Y5 -selective agonists resulted in significantly less mean seizure suppression (37.4% and 53.9%, respectively) than NPY (83.2%; P < 0.05), while the Y2 agonist had similar effects to NPY (62.3% suppression, P = 0.57). Food intake was not increased following injection of the Y2 agonist, while significant increases in food intake were seen following NPY and the other Y-subtype agonists. Compared with vehicle, NPY injection suppressed seizures following the Y1 and Y5 antagonists (45.3% and 80.1%, respectively, P < 0.05), but not following the Y2 antagonist (5.1% suppression, P = 0.46). We conclude that NPY Y2 receptors are more important than Y1 and Y5 receptors in mediating the effect of NPY to suppress absence seizures in a genetic rat model. Y2 receptor agonists may represent targets for novel drugs against genetic generalized epilepsies without resulting in appetite stimulation. [source] Withanoside IV and its active metabolite, sominone, attenuate A,(25,35)-induced neurodegenerationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Tomoharu Kuboyama Abstract At the present, medication of dementia is limited to symptomatic treatments such as the use of cholinesterase inhibitors. To cure dementia completely, that is regaining neuronal function, reconstruction of neuronal networks is necessary. Therefore, we have been exploring antidementia drugs based on reconstructing neuronal networks in the damaged brain and found that withanoside IV (a constituent of Ashwagandha; the root of Withania somnifera) induced neurite outgrowth in cultured rat cortical neurons. Oral administration of withanoside IV (10 µmol/kg/day) significantly improved memory deficits in A,(25,35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone (1 µm) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 µm A,(25,35). These data suggest that orally administrated withanoside IV may ameliorate neuronal dysfunction in Alzheimer's disease and that the active principle after metabolism is sominone. [source] Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine toleranceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004Kazuaki Yokoyama Abstract Morphine is the drug of choice to treat intractable pain, although prolonged administration often causes undesirable side-effects including analgesic tolerance. It is speculated that voltage-dependent Ca2+ channels (VDCCs) play a key role in morphine analgesia and tolerance. To examine the subtype specificity of VDCCs in these processes, we analysed mice lacking N-type (Cav2.2) or R-type (Cav2.3) VDCCs. Systemic morphine administration or exposure to warm water swim-stress, known to induce endogenous opioid release, resulted in greater analgesia in Cav2.3,/, mice than in controls. Moreover, Cav2.3,/, mice showed resistance to morphine tolerance. In contrast, Cav2.2,/, mice showed similar levels of analgesia and tolerance to control mice. Intracerebroventricular (i.c.v.) but not intrathecal (i.t.) administration of morphine reproduced the result of systemic morphine in Cav2.3,/, mice. Furthermore, i.c.v. administration of an R-type channel blocker potentiated morphine analgesia in wild-type mice. Thus, the inhibition of R-type Ca2+ current could lead to high-efficiency opioid therapy without tolerance. [source] Metabotropic glutamate receptor 5 localized in the limbic forebrain is critical for the development of morphine-induced rewarding effect in miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2004Takeshi Aoki Abstract The aim of the present study was to clarify the role of the metabotropic glutamate 5 (mGlu5) receptor subtype in the development of rewarding effect induced by a prototypical µ-opioid receptor agonist morphine in the mouse. In the conditioned place preference paradigm, intracerebroventricular (i.c.v.) administration of a selective mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), attenuated the morphine-induced rewarding effects. Using immunoblot analysis, we confirmed that the increased level of protein kinase C, (PKC,) isoform was observed in the limbic forebrain of ICR mice conditioned with morphine. Here we found for the first time that the treatment with MPEP significantly inhibited the up-regulation of PKC, isoform in the limbic forebrain of mice showing the significant place preference. Furthermore, it should be mentioned that the protein level of mGlu5 was significantly increased in membrane preparations of the limbic forebrain obtained from morphine-conditioned mice compared to those from saline-conditioned mice. As well as the result from the immunoblot analysis, we demonstrated using the receptor binding assay that the number of mGlu5 receptors in the mouse limbic forebrain was significantly increased by morphine conditioning. The present data provide direct evidence that the activation of mGlu5 receptor linked to the increased PKC, isoform in the mouse limbic forebrain is implicated in the development of rewarding effect of morphine. [source] Differential roles of corticotropin-releasing factor receptor subtypes 1 and 2 in opiate withdrawal and in relapse to opiate dependenceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2000Lin Lu Abstract The possible effects on the morphine withdrawal signs of the nonspecific corticotropin-releasing factor (CRF) receptor antagonist ,-helical CRF, the selective CRF receptor subtype 1 antagonist CP-154,526 and the selective CRF receptor subtype 2 antagonist antisauvagine-30 (AS-30) were investigated in rats. The most withdrawal signs, including jumping, teeth chatter, writhing, shakes, lacrimation, piloerection, irritability and diarrhoea, were attenuated by pretreatment with ,-helical CRF (10 µg i.c.v.) and CP-154,526 (30 mg/kg i.p.). However, no morphine withdrawal signs except for diarrhea were significantly affected by pretreatment with AS-30 (10 µg, i.c.v.). To investigate the possible role of different CRFR antagonists (,-helical CRF, CP-154,526 and AS-30) in relapse to opiate dependence, the 28-day extinction of morphine-conditioned place preference (CPP) was used. The morphine-CPP disappeared following a 28-day extinction and then was reactivated by a single injection of 10 mg/kg morphine. Pretreatment with ,-helical CRF (10 µg, i.c.v.) and CP-154,526 (30 mg/kg, i.p.) could significantly block this reactivation of morphine-CPP. In contrast, pretreatment with AS-30 (1 or 10 µg i.c.v.) did not affect this reactivation of morphine-CPP. The present study demonstrated that activation of the CRF receptor is involved in morphine withdrawal signs and relapse to morphine dependence, and that the role of CRF receptor subtypes 1 and 2 in withdrawal and reactivation of morphine dependence is not identical. CRF receptor subtype 1, but not subtype 2, is largely responsible for the action of the CRF system on opiate dependence. These results suggest that the CRF receptor antagonists, particularly the CRF receptor subtype 1 antagonist, might be of some value in the treatment and prevention of drug dependence. [source] Central nitric oxide blocks vasopressin, oxytocin and atrial natriuretic peptide release and antidiuretic and natriuretic responses induced by central angiotensin II in conscious ratsEXPERIMENTAL PHYSIOLOGY, Issue 5 2007Wagner Luis Reis The presence of nitric oxide synthase (NOS), the enzyme that catalyses the formation of nitric oxide (NO), in the circumventricular organs and magnocellular neurones suggests an important role of NO in the modulation of vasopressin (AVP) and oxytocin (OT) release. Intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) stimulates the release of AVP, OT and atrial natriuretic peptide (ANP), with the resultant antidiuretic and natriuretic effects. This study investigated the interaction between nitrergic and angiotensinergic pathways on the release of AVP, OT and ANP and on urinary volume and sodium excretion in water-loaded rats. Unanaesthetized, freely moving, male Wistar rats received two water loads followed by an injection into the lateral ventricle of an inhibitor of NOS (l -NAME), a NO donor [3-morpholinylsydnoneimine chloride (SIN-1) or S -nitroso- N -acetyl penicillamine (SNAP)] or vehicle (isotonic saline) and, 20 min after, they received a second i.c.v. injection of Ang II or vehicle. Injections of l -NAME or Ang II produced an increase in plasma levels of AVP, OT and ANP, a reduction in urinary volume and an increase in sodium excretion. Pretreatment with l -NAME enhanced the Ang II-induced increase in AVP, OT and ANP release, as well as the antidiuresis and natriuresis. Injection of SIN-1 or SNAP did not modify hormonal plasma levels and urinary parameters. In contrast SNAP blocked the AVP, OT and ANP release, as well as antidiuretic and natriuretic responses induced by ANG-II. Thus, the central nitrergic system can act to inhibit AVP, OT and ANP secretion and the antidiuretic and natriuretic effects in response to Ang II. [source] CDP-choline increases plasma ACTH and potentiates the stimulated release of GH, TSH and LH: the cholinergic involvementFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2004Sinan Cavun Abstract In the present study, we investigated the effect of intracerebroventricular (i.c.v.) administration of cytidine-5,-diphosphate (CDP) choline on plasma adrenocorticotropin (ACTH), serum growth hormone (GH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in conscious rats. The involvement of cholinergic mechanisms in these effects was also determined. In basal conditions, CDP-choline (0.5, 1.0 and 2.0 ,mol, i.c.v.) increased plasma ACTH levels dose- and time-dependently, but it did not affect the TSH, GH, FSH and LH levels. In stimulated conditions, i.c.v. administration of CDP-choline (1 ,mol, i.c.v.) produced an increase in clonidine-stimulated GH, thyrotyropin-releasing hormone (TRH)-stimulated TSH, LH-releasing hormone (LHRH)-stimulated LH, but not FSH levels. Injection of equimolar dose of choline (1 ,mol, i.c.v.) produced similar effects on hormone levels, but cytidine (1 ,mol, i.c.v.) failed to alter plasma levels of these hormones. Pretreatment with hemicholinium-3, a neuronal high affinity choline uptake inhibitor, (20 ,g, i.c.v.) completely blocked the observed hormone responses to CDP-choline. The increase in plasma ACTH levels induced by CDP-choline (1 ,mol, i.c.v.) was abolished by pretreatment with mecamylamine, a nicotinic receptor antagonist, (50 ,g, i.c.v.) but not atropine, a muscarinic receptor antagonist, (10 ,g, i.c.v.). The increase in stimulated levels of serum TSH by CDP-choline (1 ,mol, i.c.v.) was blocked by atropine but not by mecamylamine pretreatment. However, CDP-choline induced increases in serum GH and LH levels were greatly attenuated by both atropine and mecamylamine pretreatments. The results show that CDP-choline can increase plasma ACTH and produce additional increases in serum levels of TSH, GH and LH stimulated by TRH, clonidine and LHRH, respectively. The activation of central cholinergic system, mainly through the presynaptic mechanisms, was involved in these effects. Central nicotinic receptors solely mediated the increase in plasma ACTH levels while the activation of central muscarinic receptors was involved in the increase in TSH levels. Both muscarinic and nicotinic receptor activations, separately, mediated the increases in serum GH and LH levels after CDP-choline. [source] Involvement of the somatostatin-2 receptor in the anti-convulsant effect of angiotensin IV against pilocarpine-induced limbic seizures in ratsJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Bart Stragier Abstract The anti-convulsant properties of angiotensin IV (Ang IV), an inhibitor of insulin-regulated aminopeptidase (IRAP) and somatostatin-14, a substrate of IRAP, were evaluated in the acute pilocarpine rat seizure model. Simultaneously, the neurochemical changes in the hippocampus were monitored using in vivo microdialysis. Intracerebroventricularly (i.c.v.) administered Ang IV or somatostatin-14 caused a significant increase in the hippocampal extracellular dopamine and serotonin levels and protected rats against pilocarpine-induced seizures. These effects of Ang IV were both blocked by concomitant i.c.v. administration of the somatostatin receptor-2 antagonist cyanamid 154806. These results reveal a possible role for dopamine and serotonin in the anti-convulsant effect of Ang IV and somatostatin-14. Our study suggests that the ability of Ang IV to inhibit pilocarpine-induced convulsions is dependent on somatostatin receptor-2 activation, and is possibly mediated via the inhibition of IRAP resulting in an elevated concentration of somatostatin-14 in the brain. [source] Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathwayJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Melita Salkovic-Petrisic Abstract The insulin-resistant brain state is related to late-onset sporadic Alzheimer's disease, and alterations in the insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain. These findings have not been confirmed in an experimental model related to sporadic Alzheimer's disease, for example rats showing a neuronal IR deficit subsequent to intracerebroventricular (i.c.v.) treatment with streptozotocin (STZ). In this study, western blot analysis performed 1 month after i.c.v. injection of STZ showed an increase of 63% in the level of phosphorylated glycogen synthase kinase-3,/, (pGSK-3,/,) protein in the rat hippocampus, whereas the levels of the unphosphorylated form (GSK-3,/,) and protein kinase B (Akt/PKB) remained unchanged. Three months after STZ treatment, pGSK-3,/, and Akt/PKB levels tended to decrease (by 8 and 9% respectively). The changes were region specific, as a different pattern was found in frontal cortex. Structural alterations were also found, characterized by ,-amyloid peptide-like aggregates in brain capillaries of rats treated with STZ. Similar neurochemical changes and cognitive deficits were recorded in rats treated with i.c.v. 5-thio- d -glucose, a blocker of glucose transporter (GLUT)2, a transporter that is probably involved in brain glucose sensing. The IR signalling cascade alteration and its consequences in rats treated with STZ are similar to those found in humans with sporadic Alzheimer's disease, and our results suggest a role for GLUT2 in Alzheimer's pathophysiology. [source] Lorenzo's oil, adrenoleukodystrophy, and the blood, brain barrierJOURNAL OF NEUROCHEMISTRY, Issue 2002E. J. Murphy Adrenoleukodystrophy is a rapid, progressive demyelinating disease affecting the CNS that is characterized by large increases in plasma and tissue very long saturated fatty acids (VLCFA). Lorenzo's oil (LO), consisting of erucic (22:1 n-9) and oleic (18:1 n-9) acid in a triglyceride form, is a dietary therapy effective in reducing plasma and tissue VLCFA. Despite the decreased VLCFA, clinical studies indicated that LO failed to stop the progressive demyelination, suggesting that erucic acid, the active component of LO, did not cross the BBB. We addressed this question by infusing [14-14C] 22:1 n-9 (170 ,Ci/kg) into male rats using two different infusion paradigms. The radiotracer was infused (i.v.) into awake, adult male rats over a 10-min period or infused (i.c.v.) into the fourth ventricle over a 7-day period using an osmotic mini-pump. Brains were removed from the cranium, frozen in liquid nitrogen, lipids extracted, and separated using standard techniques. [1-14C] 20:4 n-6 was infused (i.v.) and used as a positive control. Following i.v. infusion, 0.011% of the erucic acid was extracted by the brain, compared to 0.055% of the arachidonic acid. About 60% of the brain erucic acid was found in the aqueous fraction compared to 30% for arachidonic acid. Further, erucic acid was targeted to cholesteryl ester and triacylglyceride pools, whereas arachidonic acid was targeted to phospholipid pools. In animals infused i.c.v., 0.078% of the dose was taken up and about 60% of the erucic acid was targeted to phospholipid pools. These results clearly demonstrate that erucic acid crosses the BBB, similar to arachidonic acid, and is incorporated into specific lipid pools. Acknowledgements:, This work was supported by The Myelin Project. [source] Long-term Infusion of Brain-Derived Neurotrophic Factor Reduces Food Intake and Body Weight via a Corticotrophin-Releasing Hormone Pathway in the Paraventricular Nucleus of the HypothalamusJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2010M. Toriya Brain-derived neurotrophic factor (BDNF) has been implicated in learning, depression and energy metabolism. However, the neuronal mechanisms underlying the effects of BDNF on energy metabolism remain unclear. The present study aimed to elucidate the neuronal pathways by which BDNF controls feeding behaviour and energy balance. Using an osmotic mini-pump, BDNF or control artificial cerebrospinal fluid was infused i.c.v. at the lateral ventricle or into the paraventricular nucleus of the hypothalamus (PVN) for 12 days. Intracerebroventricular BDNF up-regulated mRNA expression of corticotrophin-releasing hormone (CRH) and urocortin in the PVN. TrkB, the receptor for BDNF, was expressed in the PVN neurones, including those containing CRH. Both i.c.v. and intra-PVN-administered BDNF decreased food intake and body weight. These effects of BDNF on food intake and body weight were counteracted by the co-administration of ,-helical-CRH, an antagonist for the CRH and urocortin receptors CRH-R1/R2, and partly attenuated by a selective antagonist for CRH-R2 but not CRH-R1. Intracerebroventricular BDNF also decreased the subcutaneous and visceral fat mass, adipocyte size and serum triglyceride levels, which were all attenuated by ,-helical-CRH. Furthermore, BDNF decreased the respiratory quotient and raised rectal temperature, which were counteracted by ,-helical-CRH. These results indicate that the CRH-urocortin-CRH-R2 pathway in the PVN and connected areas mediates the long-term effects of BDNF to depress feeding and promote lipolysis. [source] Isolation and Characterisation of Four cDNAs Encoding Neuromedin U (NMU) From the Brain and Gut of Goldfish, and the Inhibitory Effect of a Deduced NMU on Food Intake and Locomotor ActivityJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2008K. Maruyama In rodents, neuromedin U (NMU; U for its original effects examined in the uterus) is a multifunctional neuropeptide implicated in the regulation of the circulatory and digestive systems and energy homeostasis, especially appetite. However, there is no available information on the nature and physiological roles of NMU in fish. Therefore, we attempted to isolate and characterise transcripts encoding NMU from the brain and gut of the goldfish, and to examine the involvement of NMU in the regulation of feeding behaviour in this species. We identified four cDNAs encoding three NMU orthologs from the brain and gut. Putative peptides consisting of 21, 25 and 38 amino acid residues (NMU-21, NMU-25 and NMU-38) were deduced from their nucleotide sequences. Two mRNAs for NMU-25 were strongly expressed in the gut and weakly expressed in the brain and testis. By contrast, mRNA for NMU-21 was strongly expressed in the brain and weakly expressed in the peripheral tissues. Expression of mRNA for NMU-38 was weakly expressed only in the brain. Therefore, we examined the effect of feeding status on the expression of NMU-21 mRNA in the brain. Fasting for 7 days induced a significant decrease in the expression levels of NMU-21 mRNA in the brain. We also synthesised NMU-21 after deducing its C-terminal amide from the NMU-21 mRNA, and then investigated the effect of intracerebroventricular (i.c.v.) administration of NMU-21 on food intake and locomotor activity in the goldfish. NMU-21, injected i.c.v., suppressed food intake and locomotor activity in a dose-dependent manner. These results suggest that NMU orthologs exist in fish, and that the NMU-21 deduced from them can potently inhibit food intake and locomotor activity in goldfish. [source] Thyrotrophin-Releasing Hormone Decreases Feeding and Increases Body Temperature, Activity and Oxygen Consumption in Siberian HamstersJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2007S. Schuhler Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5,50 mg/kg body weight; i.p.) and central (0.5 µg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function. [source] Hypocretin-1 Dose-Dependently Modulates Maternal Behaviour in MiceJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006K. L. D'Anna Increases in neuronal activity of hypocretin (HCRT), a peptide involved in arousal, and in HCRT-1 receptor mRNA expression have recently been identified in association with lactation. HCRT is released within brain regions regulating maternal behaviour and it is possible that increased HCRT neurotransmission during lactation supports maternal care. The present study examined for the first time the behavioural effects of HCRT on lactating mice. At intermediate doses, intracerebroventricular (i.c.v.) injections of HCRT-1 (0.06 and 0.1 µg) elevated levels of licking and grooming of pups (but not self-grooming) and number of nursing bouts without affecting other behaviours. At the highest dose, HCRT-1 (0.3 µg, i.c.v) delayed latency to nurse, decreased nursing, increased time off nest, and decreased maternal aggression. Intraperitoneal injections of the HCRT-1 receptor antagonist, SB-334867, exhibited a general trend towards increasing time spent low-arched back nursing (P = 0.053) and decreasing licking and grooming of pups while high-arched back nursing (P = 0.052). This suggests that the endogenous release of HCRT, working independently or dependently with other neuromodulators, may be necessary for full maternal behaviour expression. Possible sites of HCRT action in enhancing and impairing maternal care were identified via examinations of c,Fos immunoreactivity in association with i.c.v. HCRT injections. Together, these finding support the idea of HCRT modulating maternal behaviour, with intermediate levels (0.06 and 0.1 µg) supporting (even augmenting) some behaviours, but with levels that are too high (0.3 µg HCRT, i.c.v.), maternal behaviour and aggression are suppressed. [source] Differential Role of Corticotrophin-Releasing Factor Receptor Types 1 and 2 in Stress-Induced Suppression of Pulsatile Luteinising Hormone Secretion in the Female RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006X. F. Li Corticotrophin-releasing factor (CRF) plays a pivotal role in stress-induced suppression of the gonadotrophin-releasing hormone pulse generator. We have previously shown that type 2 CRF receptors (CRF2) mediate restraint stress-induced suppression of luteinising hormone (LH) pulses in the rat. The present study aimed: (i) to determine whether type 1 CRF receptors (CRF1) are also involved in this response to restraint and (ii) to investigate the differential involvement of CRF1 and CRF2 in the suppression of LH pulses in response to the metabolic perturbation of insulin-induced hypoglycemia and the innate immunological challenge of lipopolysaccharide (LPS). Ovariectomised rats with oestrogen replacement were implanted with intracerebroventricular (i.c.v.) and intravenous (i.v.) cannulae. Blood samples (25 µl) were collected every 5 min for 5 h for LH measurement. After 2 h of controlled blood sampling, rats were either exposed to restraint (1 h) or injected intravenously with insulin (0.25 IU/kg) or LPS (5 µg/kg). All three stressors suppressed LH pulses. The CRF1 antagonist SSR125543Q (11.5 µmol/rat i.v., 30 min before stressor) blocked the inhibitory response to restraint, but not hypoglycaemia or LPS stress. In addition to its effect on restraint, the CRF2 antagonist astressin2 -B (28 nmol/rat i.c.v., 10 min before insulin or LPS) blocked hypoglycaemia or LPS stress-induced suppression of LH pulses. These results suggest that hypoglycaemia and LPS stress-induced LH suppression involves activation of CRF2 while restraint stress-induced inhibition of LH pulses involves both CRF1 and CRF2. [source] Intracerebroventricular Injections of Prolactin Counteract the Antagonistic Effect of Bromocriptine on Rabbit Maternal BehaviourJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2004G. González-Mariscal Abstract To investigate the participation of prolactin in nest-building and maternal behaviour in rabbits, we administered (from pregnancy day 26 to parturition) rabbit prolactin (rbPRL; or vehicle) intracerebroventricularly (i.c.v.) to primiparous animals injected with bromocriptine subcutaneously (s.c.). Control females (given vehicle s.c. and i.c.v.) built a maternal nest (of straw and body hair) in 77% of cases. This proportion decreased to 19% in the bromocriptine-only group (P < 0.05) and increased to 93% in the group given bromocriptine plus rbPRL (P > 0.05). Maternal behaviour (i.e. the adoption of a crouching posture over the litter inside the nest box) was expressed by 77% of control rabbits, 19% of bromocriptine-only animals (P < 0.05) and 57% of females given bromocriptine plus rbPRL (P > 0.05). Values of nonmaternal activities (i.e. scent-marking, ambulation in an open field) were similar among the three studied groups. These results suggest that prolactin, acting in late pregnancy, plays a major role in the stimulation of nest-building and maternal behaviour in rabbits. [source] Roles of Corticotropin-Releasing Factor, Neuropeptide Y and Corticosterone in the Regulation of Food Intake In Xenopus laevisJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2004E. J. Crespi Abstract In mammals, hypothalamic control of food intake involves counterregulation of appetite by anorexigenic peptides such as corticotropin-releasing factor (CRF), and orexigenic peptides such as neuropeptide Y (NPY). Glucocorticoids also stimulate food intake by inhibiting CRF while facilitating NPY actions. To gain a better understanding of the diversity and evolution of neuroendocrine feeding controls in vertebrates, we analysed the effects of CRF, NPY and glucocorticoids on food intake in juvenile Xenopus laevis. We also analysed brain CRF and NPY mRNA content and plasma corticosterone concentrations in relation to nutritional state. Intracerebroventricular (i.c.v.) injection of ovine CRF suppressed food intake while CRF receptor antagonist ,helical CRF(9,41) significantly increased food intake relative to uninjected and placebo controls. By contrast, i.c.v. injection of frog NPY and short-term corticosterone treatment increased food intake. Semi-quantitative reverse transcription-polymerase chain reaction analyses showed that CRF and NPY mRNA fluctuated with food intake in the brain region containing the mid-posterior hypothalamus, pretectum, and optic tectum: CRF mRNA decreased 6 h after a meal and remained low through 31 days of food deprivation; NPY mRNA content also decreased 6 h after a meal, but increased to prefeeding levels by 24 h. Plasma corticosterone concentration increased 6 h after a meal, returned to prefeeding levels by 24 h, and did not change with prolonged food deprivation. This postprandial increase in plasma corticosterone may be related to the subsequent increase in plasma glucose and body water content that occurs 24 h postfeeding. Overall, our data support the conclusion that, similar to other vertebrates, CRF is anorexigenic while NPY is orexigenic in X. laevis, and CRF secretion modulates food intake in the absence of stress by exerting an inhibitory tone on appetite. Furthermore, the stress axis is activated in response to food intake, but in contrast to mammals and birds is not activated during periods of food deprivation. [source] Opioid Receptor Subtypes Involved in the Regulation of Prolactin Secretion During Pregnancy and LactationJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2003Z. B. Andrews Abstract Afferent endogenous opioid neuronal systems facilitate prolactin secretion in a number of physiological conditions including pregnancy and lactation, by decreasing tuberoinfundibular dopamine (TIDA) inhibitory tone. The aim of this study was to investigate the opioid receptor subtypes involved in regulating TIDA neuronal activity and therefore facilitating prolactin secretion during early pregnancy, late pregnancy and lactation in rats. Selective opioid receptor antagonists nor-binaltorphimine (, -receptor antagonist, 15 µg/5 µl), beta funaltrexamine (, -receptor antagonist, 5 µg/5 µl) and naltrindole (, -receptor antagonist, 5 µg/5 µl) or saline were administered intracerebroventricularly (i.c.v.) on day 8 of pregnancy during a nocturnal prolactin surge, on day 21 of pregnancy during the ante partum prolactin surge or on day 7 of lactation before the onset of a suckling stimulus. Serial blood samples were collected at regular time intervals, via chronic indwelling jugular cannulae, before and after drug administration and plasma prolactin was determined by radioimmunoassay. TIDA neuronal activity was measured using the 3,4-dihydroxyphenylacetic acid (DOPAC) : dopamine ratio in the median eminence 2 h 30 min after i.c.v. drug injection. In each experimental condition, plasma prolactin was significantly inhibited by both , - and , -receptor antagonists, whereas the , -receptor antagonist had no effect compared to saline-injected controls. Similarly, nor-binaltorphimine and beta funaltrexamine significantly increased the median eminence DOPAC : dopamine ratio during early and late pregnancy, and lactation whereas naltrindole had no effect compared to saline-injected controls. These data suggest that TIDA neuronal activity, and subsequent prolactin secretion, is regulated by endogenous opioid peptides acting at both , - and , -opioid receptors during prolactin surges of early pregnancy, late pregnancy and lactation. [source] Effect of Intracerebroventricular Administration of the Octadecaneuropeptide on the Expression of Pro-Opiomelanocortin, Neuropeptide Y and Corticotropin-Releasing Hormone mRNAs in Rat HypothalamusJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2003V. Compère Abstract Intracerebroventricular (i.c.v.) administration of the octadecaneuropeptide (diazepam-binding inhibitor [33,50]; ODN) exerts a potent anorexigenic effect in the rat. We studied the effect of ODN on three neuropeptides involved in feeding behaviour: the orexigenic peptide neuropeptide Y (NPY) and two anorexigenic peptides, corticotropin-releasing hormone (CRH) and the pro-opiomelanocortin (POMC)-derived peptide , -melanocyte-stimulating hormone. The effect of i.c.v. administration of ODN (0.1 µg/kg and 1 µg/kg) on mRNA expression of the peptides in male rat hypothalamus was evaluated by semiquantitative in situ hybridization. In the arcuate nucleus, NPY-expressing neurones were mostly found in the inner zone in close proximity of the third ventricle. ODN at the dose of 0.1 µg/kg induced a significant decrease of 17.4% in NPY mRNA expression, while the depressing effect was more marked (31.4%) with the highest dose of ODN (1 µg/kg). POMC-expressing neurones were more laterally located in the arcuate nucleus. Administration of ODN at 0.1 µg/kg and 1 µg/kg doses induced increases of 33.5% and 27.4% in POMC mRNA expression, respectively. Labelling obtained with the CRH cRNA probe was essentially distributed throughout the medial parvocellular area of the hypothalamic paraventricular nucleus. ODN, at doses of 0.1 and 1 µg/kg, resulted in 17.8% and 32.8% decreases in CRH mRNA expression, respectively. The present data suggest that ODN might exert its anorexigenic effect by increasing mRNA expression of POMC and decreasing mRNA expression of NPY in the arcuate nucleus. [source] Anorexic But Not Pyrogenic Actions of Interleukin-1 are Modulated by Central Melanocortin-3/4 Receptors in the RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2001C. B. Lawrence Abstract The cytokine interleukin-1 (IL-1), which mediates many responses to infection and injury, induces anorexia and fever through direct actions in the central nervous system. The melanocortin neuropeptides, such as alpha melanocyte-stimulating hormone (,-MSH), reportedly antagonize many actions of IL-1, including fever and anorexia. However, it is unknown whether endogenous melanocortins modulate anorexia induced by IL-1. The objective of the present study was to establish the effect of endogenous melanocortins on IL-1-induced anorexia and fever in the rat. Intracerebroventricular (i.c.v.) injection of IL-1, caused a significant reduction in food intake and body weight gain, and a rise in core body temperature in conscious rats. Coadministration of the melanocortin-3/4 receptor (MC3/4-R) antagonist, SHU9119, reversed IL-1,-induced reductions in food intake and body weight, but did not affect the febrile response to IL-1,. These data suggest IL-1, may elicit its effects on food intake through the melanocortin system, predominantly via the MC3-R or MC4-R. In contrast, IL-1,-induced fever does not appear to be mediated or modulated by MC3-R or MC4-R activity. [source] Neuropeptide Y Counteracts the Anorectic and Weight Reducing Effects of Ciliary Neurotropic FactorJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2000S. Pu Abstract Ciliary neurotrophic factor (CNTF), a cytokine of the interleukin-6 superfamily, has been shown to induce hypophagia and weight loss. Neuropeptide Y (NPY) and orexin are potent orexigenic signals in the hypothalamus. Anorexia, normally seen in response to infection, injury and inflammation, may result from diminished hypothalamic orexigenic signalling caused by persistently elevated cytokines, including CNTF. To test this hypothesis, we first examined the effects of chronic intracerebroventricular (i.c.v.) infusion of CNTF for 6,7 days on food intake and body weight as well as hypothalamic NPY and orexin gene expression in male rats. Subsequently, the effectiveness of NPY replacement to counteract the effects of CNTF by coinfusion of NPY and CNTF was evaluated. Chronic i.c.v. infusion of CNTF (2.5 µg/day) reduced body weight (14.3% vs control) at the end of 7 days. Food intake remained suppressed for 5 days postinfusion and subsequently gradually returned to the control range by day 7. Serum leptin concentrations in these rats were in the same range seen in control rats. Chronic i.c.v. infusion of higher doses of CNTF (5.0 µg/day) produced sustained anorexia and body weight loss (29% vs controls) through the entire duration of the experiment. This severe anorexia was accompanied by markedly suppressed serum leptin concentrations. Furthermore, CNTF infusion alone significantly reduced hypothalamic NPY gene expression (P < 0.05) without affecting orexin gene expression. As expected, in fusion of NPY alone (18 µg/day) augmented food intake (191.6% over the initial control, P < 0.05) and produced a 25.1% weight gain in conjunction with a 10-fold increase in serum leptin concentrations at the end of the 7-day period. Interestingly, coinfusion of this regimen of NPY with the highly effective anorectic and body reducing effects of CNTF (5.0 µg/day) not only prevented the CNTF-induced anorexia and weight loss, but also normalized serum leptin concentrations and hypothalamic NPY gene expression. These results demonstrate that chronic central infusion to produce a persistent elevation of the cytokine at pathophysiological levels (a situation that may normally manifest during infection, injury and inflammation) produced severe anorexia and weight loss in conjunction with reduction in both serum leptin concentrations and hypothalamic NPY gene expression. Reinstatement of hypothalamic NPY signalling by coinfusion of NPY counteracted these CNTF-induced responses. [source] In Vivo Modulation of Post-Spike Excitability in Vasopressin Cells by ,-Opioid Receptor ActivationJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2000C. H. Brown Abstract An endogenous ,-opioid agonist reduces the duration of phasic bursts in vasopressin cells. Non-synaptic post-spike depolarizing after-potentials underlie activity during bursts by increasing post-spike excitability and ,-receptor activation reduces depolarizing after-potential amplitude in vitro. To investigate the effects of ,-opioids on post-spike excitability in vivo, we analysed extracellular recordings of the spontaneous activity of identified supraoptic nucleus vasopressin cells in urethane-anaesthetized rats infused with Ringer's solution (n = 17) or the ,-agonist, U50,488H (2.5 µg/h at 0.5 µl/h; n = 23), into the supraoptic nucleus over 5 days. We plotted the mean hazard function for the interspike interval distributions as a measure of the post-spike excitability of these cells. Following each spike, the probability of another spike firing in vasopressin cells recorded from U50,488H infused nuclei was markedly reduced compared to Ringer's treated vasopressin cells. To determine whether U50,488H could reduce post-spike excitability in cells that displayed spontaneous phasic activity, we infused U50,488H (50 µg/h at 1 µl/h, i.c.v.), for 1,12 h while recording vasopressin cell activity. Nine of 10 vasopressin cells were silenced by i.c.v. U50,488H 15 ± 5 min into the infusion. Six cells exhibited spontaneous phasic activity before U50,488H infusion and recordings from three of these phasic cells were maintained until activity recovered; during U50,488H infusion, the activity of these three cells was irregular. Generation of the mean hazard function before and during U50,488H infusion revealed a reduction in post-spike excitability during U50,488H infusion. Thus, ,-receptor activation reduces post-spike excitability in vivo; this may reflect inhibition of depolarizing after-potentials and may thus underlie the reduction in burst duration of vasopressin cells caused by an endogenous ,-agonist in vivo. [source] Pain relief by gabapentin and pregabalin via supraspinal mechanisms after peripheral nerve injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2008Mitsuo Tanabe Abstract The antihypersensitivity actions of gabapentin and pregabalin have been well characterized in a large number of studies, although the underlying mechanisms have yet to be defined. We have been focusing on the supraspinal structure as a possible site for their action and have demonstrated that intracerebroventricular (i.c.v.) administration of gabapentin and pregabalin indeed decreases thermal and mechanical hypersensitivity in a murine chronic pain model involving partial ligation of the sciatic nerve. This novel supraspinally mediated analgesic effect was markedly suppressed by either depletion of central noradrenaline (NA) or blockade of spinal ,2 -adrenergic receptors. Moreover, i.c.v. injection of gabapentin and pregabalin increased spinal NA turnover in mice only after peripheral nerve injury. In locus coeruleus (LC) neurons in brainstem slices prepared from mice after peripheral nerve injury, gabapentin reduced the ,-aminobutyric acid (GABA) type A receptor-mediated inhibitory postsynaptic currents (IPSCs). Glutamate-mediated excitatory synaptic transmission was hardly affected. Moreover, gabapentin did not reduce IPSCs in slices taken from mice given a sham operation. Although gabapentin altered neither the amplitude nor the frequency of miniature IPSCs, it reduced IPSCs together with an increase in the paired-pulse ratio, suggesting that gabapentin acts on the presynaptic GABAergic nerve terminals in the LC. Together, the data suggest that gabapentin presynaptically reduces GABAergic synaptic transmission, thereby removing the inhibitory influence on LC neurons only in neuropathic pain states, leading to activation of the descending noradrenergic system. © 2008 Wiley-Liss, Inc. [source] Intracerebroventricular administration of GABA-A and GABA-B receptor antagonists attenuate feeding and sleeping-like behavior induced by L -pipecolic acid in neonatal chicksJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003T. Takagi Abstract It has been demonstrated that L -pipecolic acid (L -PA), a major metabolic intermediate of L -lysine (L -Lys) in the mammalian and chicken brain, is involved in the functioning of the GABAergic system. A previous study has shown that intracerebroventricular (i.c.v.) injection of L -PA suppressed feeding and induced sleep-like behavior in neonatal chicks; however, the precise relationship between the GABAergic system and L -PA has not been clarified. In the present study, the role of the GABA-A or GABA-B receptors in the suppression of food intake and induction of sleeping-like behavior by L -PA was investigated. Chicks were injected i.c.v. with the GABA-A antagonist picrotoxin or GABA-B antagonist CGP54626 along with L -PA. Although suppression of food intake by L -PA was restored partially by co-injection with CGP54626, but not picrotoxin, sleep-like behavior induced by L -PA was suppressed significantly by both antagonists. These results suggested that L -PA activated both GABA-A and GABA-B receptors, and GABA-B receptors alone contributed to food intake whereas both receptors contributed to sleep-like behavior. © 2003 Wiley-Liss, Inc. [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] Inhibitory effect of oxytocin on accelerated colonic motility induced by water-avoidance stress in ratsNEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2009M. Matsunaga Abstract, Recent studies have indicated that brain and gut activities are interrelated and exposure to several stressors, such as water-avoidance stress, stimulates the motor function of the gut through corticotropin-releasing factor (CRF)-signalling pathways in the brain. Central oxytocin is known to attenuate stress responses, including CRF expression in the brain. Here, we examined whether central oxytocin attenuated the acceleration of colonic motility induced by water-avoidance stress. A force transducer was attached to the distal colon of male rat, and the colonic motility and faecal pellet output were recorded while the rats were exposed to water-avoidance stress. Intracerebroventricular (i.c.v.) injections of oxytocin (5, 50 and 500 pmol) and the oxytocin receptor antagonist tocinoic acid (25 ,g) were administered before exposure to water-avoidance stress, and the effect of oxytocin on colonic motor function was determined. Centrally administered oxytocin inhibited the accelerated colonic motility induced by water-avoidance stress. The effective dose ranged between 5 and 50 pmol on i.c.v. injection. Oxytocin also decreased the number of CRF-positive cells in the paraventricular nucleus and corticosterone release. The inhibitory effect of oxytocin on accelerated colonic motility was blocked by pretreatment with oxytocin receptor antagonist. Furthermore, centrally administered tocinoic acid enhanced the acceleration of colonic motility. These results suggested that endogenous central oxytocin may contribute to the regulation of colonic function and inhibit the brain CRF-signalling pathways targeting the gut, resulting in the inhibition of stress-induced colonic contractions. [source] Central and peripheral role of the nociceptin/orphaninFQ system on normal and disturbed colonic motor function and faecal pellet output in the ratNEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2008M. Broccardo Abstract, In this study, seeking further information on the role of the nociceptin/orphanin FQ (N/OFQ)-ergic system in normal and disturbed colonic motor function in rats, we compared the colonic effects of UFP-112, a novel highly potent agonist, with those of N/OFQ. When injected intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.), UFP-112 and N/OFQ increased bead expulsion time in a statistically significant and dose-related manner and reduced the percentage of rats with castor oil-induced diarrhoea. UFP-112 showed greater efficacy, higher potency and longer-lasting inhibitory effects than N/OFQ, and pretreatment with UFP-101, a selective antagonist, blocked the N/OFQ analogue-induced responses in both tests. When injected i.c.v., UFP-112 and N/OFQ inhibited corticotrophin releasing factor- and restrain stress-stimulated faecal pellet excretion significantly and in a dose-related manner. Conversely, when injected peripherally both peptides significantly inhibited colonic propulsive motility but did so in a non-dose-related manner. In conclusion, these findings indicate that, in the rat, the central and peripheral N/OFQ systems have an inhibitory role in modulating distal colonic propulsive motility under physiological and pathological conditions. UFP-112 therefore promises to be a useful pharmacological tool for investigating the role of the N/OFQ system in motor functions in the distal colonic tract under physiological and pathological conditions. [source] Improvement of bladder storage function by ,1-blocker depends on the suppression of C-fiber afferent activity in rats,NEUROUROLOGY AND URODYNAMICS, Issue 5 2006Osamu Yokoyama Abstract Aims ,1-blockers improve voiding symptoms through the reduction of prostatic and urethral smooth muscle tone; however, the underlying mechanism of improvement of storage symptoms is not known. Using a rat model of detrusor overactivity caused by cerebral infarction (CI), we undertook the present study to determine whether the effect of an ,1-blocker, naftopidil, is dependent on the suppression of C-fiber afferents. Methods To induce desensitization of C-fiber bladder afferents, we injected resiniferatoxin (0.3 mg/kg, RTX) sub-cutaneously to female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO) (RTX-CI rats). As controls we used rats without RTX treatment (CI rats). MCAO and insertion of a polyethylene catheter through the bladder dome were performed under halothane anesthesia. We investigated the effects on cystometrography (CMG) of intravenous (i.v.), intracerebroventricular (i.c.v.), or intrathecal (i.t.) administration of naftopidil in conscious CI rats. Results Bladder capacity (BC) was markedly reduced after MCAO in both RTX-CI and CI rats. I.v. administration of naftopidil significantly increased BC in CI rats without an increase in residual volume, but it had no effects on BC in RTX-CI rats. I.t. administration of naftopidil significantly increased BC in CI but not in RTX-CI rats. Conclusions These results suggest that naftopidil has an inhibitory effect on C-fiber afferents in the lumbosacral spinal cord, improving BC during the storage phase. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] Protective effect of quercetin against ICV colchicine-induced cognitive dysfunctions and oxidative damage in ratsPHYTOTHERAPY RESEARCH, Issue 12 2008Anil Kumar Abstract Intracerebroventricular (i.c.v.) administration of colchicine, a microtubule-disrupting agent, causes cognitive dysfunction and oxidative stress. The present study was designed to investigate the protective effects of quercetin against colchicine-induced memory impairment and oxidative damage in rats. An i.c.v. cannula was implanted in the lateral ventricle of male Wistar rats. Colchicine was administered at dose of 15 µg/rat. Morris water maze and plus-maze performance tests were used to assess memory tasks. Various biochemical parameters such as lipid peroxidation, reduced glutathione, nitrite level, acetylcholinesterase and proteins were also assessed. Central administration of colchicine (15 µg/rat) showed poor retention of memory. Chronic treatment with quercetin (20 and 40 mg/kg, p.o.) twice daily for a period of 25 days beginning 4 days prior to colchicine injection significantly improved the colchicine-induced cognitive impairment. Biochemical analysis revealed that i.c.v. colchicine injection significantly increased lipid peroxidation, nitrite and depleted reduced glutathione activity in the brains of rats. Chronic administration of quercetin significantly attenuated elevated lipid peroxidation and restored the depleted reduced glutathione, acetylcholinesterase activity and nitrite activity. The results of the present study clearly indicated that quercetin has a neuroprotective effect against colchicine-induced cognitive dysfunctions and oxidative damage. This article was published online on 3 November 2008. An error was subsequently identified. This notice is included in the online and print version to indicate that both have been corrected. [24 November 2008] Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||