Sex and estrous cycle variations of rat striatal dopamine uptake sites

The reuptake of dopamine into nerve terminals is the primary mechanism of inactivation of this neurotransmitter in the synaptic cleft. We report sex differences and estrous cycle variations of rat striatal dopamine uptake sites. During the estrous cycle, peak density of striatal dopamine uptake sites labelled with [3H]GBR-12935 occurred in the morning of proestrus in coincidence with peak dopamine, serotonin, dihydroxyphenylacetic acid and 5-hydroxytryptophan levels pointing to a presynaptic effect of gonadal hormones. Striatal homovanillic acid and 5-hydroxyindoleacetic acid levels as well as [3H]GBR-12935 binding affinity remained unchanged throughout the estrous cycle. The density of [3H]GBR-12935 striatal binding sites was lower in ovariectomized rats compared to intact female rats during the estrous cycle, whereas it was similar in gonadectomized male rats, intact male rats and ovariectomized rats. Binding affinity was in general similar for all the groups of rats examined. The affinity of dopamine for striatal [3H]GBR-12935 binding sites was similar in males and ovariectomized females, and did not change during the female estrous cycle. In summary, striatal dopamine uptake site density was lower in male compared to intact female rats and was shown to fluctuate during the female estrous cycle. These results suggest that gonadal hormones could influence the activity of psychoactive drugs acting on neuronal dopamine uptake sites.