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

Abstract

BACKGROUND:

The dopamine D3 receptor (DRD3) 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 DRD3 and DRD4, and interest in repurposing it for addictive disorders has grown.

METHODS:

Binding of [3H]-(+)-PHNO in the rat cerebellum and striatum was used to measure occupancy by buspirone of DRD3 or DRD2, 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 DRD2 and DRD3 at high doses and the DRD3, but not the DRD2, 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 DRD3, the effects found do not parallel those found in previous studies of the effects of selective DRD3 antagonists on the rGT. Thus, buspirone may impair performance on the rGT through actions at multiple receptor sites.

• Authors: Patricia Di Ciano, Patrick Mc Cormick, Cristiana Stefan, Ernest Wong, Aaron Kim, Gary Remington, Bernard Le Foll
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 234 Issue 22 Pg. 3309-3320 (Nov 2017) ISSN: 1432-2072 [Electronic] Germany
• PMID: 28825117 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• Receptors, Dopamine D2
• Receptors, Dopamine D3
• Receptors, Dopamine D4
• Buspirone

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Behavior, Addictive (psychology)
• Buspirone (pharmacology)
• Cerebellum (drug effects)
• Choice Behavior (drug effects)
• Corpus Striatum (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Repositioning
• Gambling (psychology)
• Male
• Rats
• Rats, Long-Evans
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Receptors, Dopamine D2 (drug effects)
• Receptors, Dopamine D3 (drug effects)
• Receptors, Dopamine D4 (drug effects)
• Reinforcement, Psychology