The role of 5-HT in the anxiogenic effects of acute ethanol withdrawal and in the long-lasting cognitive deficits.
There was a significant increase in potassium-stimulated release of 3H-[5-HT] from hippocampal slices taken from rats withdrawn from chronic ethanol treatment, compared with control-treated rats. The anxiogenic behaviour observed 12 h after ethanol withdrawal was inhibited by the 5-HT1A partial agonist, buspirone (200 micrograms/kg s.c.), indicating that the increased 5-HT release might underlie the anxiogenic response. The ex-ethanol treated rats showed impaired habituation of motor activity in the holeboard and a reduced exploratory response. The latter, but not the former, were reversed by the 5-HT3 receptor antagonist, ondansetron (0.01 microgram/kg i.p.). Ondansetron was without effect on working memory errors, but significantly increased the number of reference memory errors made by the ex-ethanol group. It also had a significantly anxiogenic effect in this group. These results suggest that the chronic ethanol treatment changes the 5-HT system and has long-lasting effects on the function of 5-HT3 receptors.
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Psychopharmacology Research Unit, Guy's Hospital, London, U.K.
Andrews
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al-Farhan
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Wu
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PY
D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D002065:Buspirone / Q000494:pharmacology; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D000431:Ethanol / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D017294:Ondansetron / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology*
D011985:Receptors, Serotonin; D012701:Serotonin; D000431:Ethanol; D017294:Ondansetron; D011188:Potassium; D002065:Buspirone