Anxiogenic behavior in rats during acute and protracted ethanol withdrawal: reversal by buspirone.
This study investigated the effectiveness of buspirone in reversing the anxiogenic behaviors occurring during ethanol withdrawal as measured in the elevated plus-maze. In response to anxiogenic drugs, rats spend less time in and make fewer entries onto the open arms of an elevated plus-maze, whereas anxiolytic drugs produce opposite effects. In this study, rats were fed a liquid diet containing 4.5% ethanol for 7 days. Twelve h (acute withdrawal) and 7 days (protracted withdrawal) following cessation of the ethanol diet, rats were tested on the elevated plus-maze. During these withdrawal periods, the percent open-arm entries and time spent on the open arms were significantly reduced relative to animals fed an ethanol-free diet, suggestive of anxiogenic-like symptoms. Buspirone (0.32-1.25 mg/kg) dose dependently reversed the withdrawal-induced decreases in open-arm activity. The anxiolytic-like activity of buspirone observed during ethanol withdrawal may be due to a reduction in serotonergic neurotransmission through activation of presynaptic 5-HT1A autoreceptors. The results obtained in this study suggest that pharmacotherapy with selective 5-HT1A agonists may be beneficial in alleviation of anxiety during ethanol withdrawal.
Lal
H
H
Department of Pharmacology, Texas College of Osteopathic Medicine, Ft. Worth 76107.
Prather
P L
PL
Rezazadeh
S M
SM
D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology*; D001522:Behavior, Animal / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013997:Time Factors
D000431:Ethanol; D002065:Buspirone