The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity.
To investigate a dopaminergic component in the discriminative stimulus properties of buspirone, rats were trained to discriminate 2.5 mg/kg buspirone from saline, using a two lever, food-rewarded, fixed ratio 10 operant procedure. To test the dopamine-2 (D2) antagonist action of buspirone, a second group of rats was trained to discriminate 0.16 mg/kg apomorphine from saline. In addition to a complete generalization to 8-OH-DPAT, the D2 antagonists haloperidol, R 79598 and sulpiride showed a partial generalization to buspirone. The benzodiazepine ligands chlordiazepoxide and bretazenil did not generalize to the buspirone cue. Buspirone (2.0 mg/kg) completely blocked the apomorphine cue in the apomorphine trained rats. Haloperidol, R 79895 and sulpiride also blocked the apomorphine cue, although at doses much smaller than the doses needed to evoke buspirone responding in the buspirone trained group. 8-OH-DPAT did not antagonize apomorphine. It was concluded that the D2 action of buspirone partially contributes to its discriminative stimulus properties. Mediation of the buspirone cue by 5-HT1a receptor activation seemed predominant. Further, buspirone can act as a full D2 antagonist in drug discrimination. A model was proposed suggesting a compound discriminative stimulus complex of buspirone with a dominant 5-HT1a component that overshadows a less pronounced D2 component.
Rijnders
H J
HJ
Department of Psychopharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Slangen
J L
JL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002065:Buspirone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D002707:Chlordiazepoxide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001058:Apomorphine; D002065:Buspirone; D008784:Methysergide