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The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity

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Abstract

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.

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  1. Department of Psychopharmacology, Faculty of Pharmacy, University of Utrecht, Sorbonnelaan 16, NL-3584 CA, Utrecht, The Netherlands

    Henk J. Rijnders & Jef L. Slangen

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  1. Henk J. Rijnders
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  2. Jef L. Slangen
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Rijnders, H.J., Slangen, J.L. The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity. Psychopharmacology 111, 55–61 (1993). https://doi.org/10.1007/BF02257407

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  • DOI: https://doi.org/10.1007/BF02257407

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