Interaction of buspirone and dopaminergic agents on punished behavior of pigeons.
The non-benzodiazepine anxiolytic buspirone was studied alone and in combination with either haloperidol or apomorphine. Drug effects were evaluated under a baseline of punished and unpunished keypeck responses of pigeons; every 30th response produced food (no punishment) in the presence of a white keylight and, when the keylight was red in alternate 3 min periods, every 30th response produced both food and a brief electric shock (punishment). Buspirone (0.03-3 mg/kg, IM) increased the low rates of punished responding to a maximum of 1000% of control at doses of 0.1-1 mg/kg. Unpunished responding was only marginally affected at lower doses and dose-dependent decreases were obtained from 1 to 10 mg/kg. Although less potent, chlordiazepoxide (1-100 mg/kg IM) produced effects which were similar to those of buspirone, a finding which contrasts with the greater efficacy of benzodiazepines for increasing punished behavior in mammals. Dose-effect functions for buspirone were unchanged by haloperidol administration (0.01 and 0.03 mg/kg, IM, 5 min prior) or by concurrent treatment with a behaviorally-ineffective dose of apomorphine (0.003 mg/kg, IM). Rate-decreasing doses of apomorphine (0.01-0.1 mg/kg) reversed the increases in punished responding produced by lower doses of buspirone (0.03 and 0.1 mg/kg) and the apomorphine-induced decreases in unpunished responding were antagonized by buspirone at doses which had little affect when given alone. The ability of buspirone to reverse the rate-decreasing effects of apomorphine on unpunished responding suggests that buspirone does exhibit dopaminergic antagonist properties in vivo. However, effects of buspirone on punished responding of pigeons do not appear to be due to dopaminergic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Witkin
J M
JM
Barrett
J E
JE
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D002065:Buspirone; D002707:Chlordiazepoxide / Q000494:pharmacology; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D011678:Punishment; D011743:Pyrimidines / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D011954:Receptors, Dopamine; D002707:Chlordiazepoxide; D006220:Haloperidol; D001058:Apomorphine; D002065:Buspirone