Abstract
the effects of quinpirole (QUIN), a preferential DRD3 agonist, in drug-naive male and female rhesus monkeys. Next, we examined the effects of chronic COC (n=3) and MA (n=3) exposure on sensitivity to QUIN in male monkeys. Finally, using PET imaging with the radioligand [11C]PHNO,weexamined the relationshipbetween DRD3 availability and (1) QUIN-elicited yawning and (2) simple discrimination and reversal performance – a measure of cognitive flexibility. Methods: Cumulative doses of QUIN (0.01–0.3mg/kg) were injected i.m. in30-minbinsand the totalnumberof yawnsobserved were recorded for each bin. QUIN-elicited yawning was characterized as an inverted U-shaped function of dose. Results: Significant sex differences were noted with QUIN being less potent and eliciting fewer yawns in females. Additionally, monkeys with a MA SA history were more sensitive to the behavioral effects of low doses of QUIN vs. controls, whereas COC SA monkeys were not significantly different than controls. Finally, analyses revealed significant relationships between DRD3 availability and both QUIN-elicited yawning and acquisition of discrimination in several regions of the brain. Future studies will extend these results to females. Conclusions: These findings suggest that QUIN-elicited yawning is an excellent tool for examining DRD3 activity, that this receptor is critical in discrimination learning, and that both sex and drug history influence individual sensitivity to the behavioral effects of DRD3 preferring compounds. Such information will be critical in developing sex-specific treatments for drug abuse. Financial support: Supported by DA012460.
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