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.
In order to assess the resistance of drug discriminative responding to prolonged reinforcement omission, rats were trained to discriminate between either 6.0 mg/kg PO or 30.0 mg/kg PO. CDP and saline, using a food reinforced (V140-FR10) operant procedure. Dose generalization tests were conducted for both groups. Sessions were then run without reinforcement while drug (D) and saline (S) administrations were continued (extinction phase). After a maximum of 30 sessions without reinforcement, or when the rats emitted less than ten responses on either lever during three successive sessions (extinction criterion), reinforcement was reinstated. Finally, additional dose generalization tests with CDP were run. The discriminative responding controlled by the D and S administrations was not affected significantly by prolonged reinforcement omission in either group. For both groups, response rates were decreased and latencies to initiate responding were increased during the extinction phase. Response rate reduction occurred more rapidly for the drug condition in the high training dose group. This group also reached the extinction criterion sooner than the low training dose group. The reacquisition process occurred very rapidly. Response rates increased substantially after the first reinforcement had been obtained. After ten reacquisition sessions, response rates and latencies had reached values similar to those observed before extinction was initiated. Data revealed no differences between groups and the course of reacquisition did not differ between the S and D conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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