Sex differences in the motor inhibitory and stimulatory role of dopamine D1 receptors in rats

Abstract

We investigated sex differences in the motor responses to the full and selective dopamine D1-like receptor agonist, (±)-6-chloro-7,8-dihydroxyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrobromide (SKF-81297; 0.3, 3, and 10 mg/kg, s.c.), in non-habituated adult rats. In general, SKF-81297 produced a biphasic effect on motor activity (including locomotion, rearing and exploratory activity) which consisted of an initial short inhibition followed by a long-lasting stimulation. These effects were dose- and sex-dependent. The inhibitory phase was more pronounced in males than females while the opposite was true for the stimulatory phase. Importantly, the motor inhibitory effects of SKF-81297 were not due to an increase in stereotypy (e.g., grooming activity). These biphasic effects on several motor parameters suggest the presence of two distinct dopamine D1 receptor populations which have opposite effects on motor activity and which are, in part, sexually dimorphic.