The effects of buspirone on occupancy of dopamine receptors and the rat gambling task.

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Bibliographic Details
Title:	The effects of buspirone on occupancy of dopamine receptors and the rat gambling task.
Authors:	Ciano, Patricia, Cormick, Patrick, Stefan, Cristiana, Wong, Ernest, Kim, Aaron, Remington, Gary, Foll, Bernard
Source:	Psychopharmacology. Nov2017, Vol. 234 Issue 22, p3309-3320. 12p.
Subjects:	Buspirone, Dopamine receptors, Drug development, Tranquilizing drugs, Laboratory rats
Abstract:	Background: The dopamine D3 receptor (DRD) has been proposed as a target for drug development for the treatment of addictive disorders. Recently, the anxiolytic buspirone has been shown to have affinity for DRD and DRD, and interest in repurposing it for addictive disorders has grown. Methods: Binding of [H]-(+)-PHNO in the rat cerebellum and striatum was used to measure occupancy by buspirone of DRD or DRD, respectively. Effects of buspirone in the rat gambling task (rGT) and the five-choice serial reaction time task (5-CSRTT) were examined. Results: Buspirone occupied both the DRD and DRD at high doses and the DRD, but not the DRD, in the narrow dose range of 3 mg/kg. At 10 mg/kg, a disruption of performance on rGT was observed. All measures of performance on the rGT, except for perseverations, were affected at 3 mg/kg. On the 5-CSRTT, omissions were increased. Impairments in the rGT were not mimicked by the effects induced by satiation. Further, buspirone did not impair food-maintained responding under a progressive ratio schedule of reinforcement at any dose, suggesting that the effects of buspirone on the rGT cannot be explained by non-selective actions. Conclusions: Although buspirone had effects on the rGT at the dose that selectively occupied the DRD, the effects found do not parallel those found in previous studies of the effects of selective DRD antagonists on the rGT. Thus, buspirone may impair performance on the rGT through actions at multiple receptor sites. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
Abstract:	Background: The dopamine D3 receptor (DRD) has been proposed as a target for drug development for the treatment of addictive disorders. Recently, the anxiolytic buspirone has been shown to have affinity for DRD and DRD, and interest in repurposing it for addictive disorders has grown. Methods: Binding of [H]-(+)-PHNO in the rat cerebellum and striatum was used to measure occupancy by buspirone of DRD or DRD, respectively. Effects of buspirone in the rat gambling task (rGT) and the five-choice serial reaction time task (5-CSRTT) were examined. Results: Buspirone occupied both the DRD and DRD at high doses and the DRD, but not the DRD, in the narrow dose range of 3 mg/kg. At 10 mg/kg, a disruption of performance on rGT was observed. All measures of performance on the rGT, except for perseverations, were affected at 3 mg/kg. On the 5-CSRTT, omissions were increased. Impairments in the rGT were not mimicked by the effects induced by satiation. Further, buspirone did not impair food-maintained responding under a progressive ratio schedule of reinforcement at any dose, suggesting that the effects of buspirone on the rGT cannot be explained by non-selective actions. Conclusions: Although buspirone had effects on the rGT at the dose that selectively occupied the DRD, the effects found do not parallel those found in previous studies of the effects of selective DRD antagonists on the rGT. Thus, buspirone may impair performance on the rGT through actions at multiple receptor sites. [ABSTRACT FROM AUTHOR]
ISSN:	00333158
DOI:	10.1007/s00213-017-4715-5