Ovarian hormone influences on the density of immunoreactivity for tyrosine hydroxylase and serotonin in the primate corpus striatum

The serotonergic and dopaminergic inputs to the corpus striatum in human and non-human primates participate in diverse sensorimotor, cognitive, and affective functions, are implicated in dysfunction in diseases such as Parkinson's disease and schizophrenia, and are targets for many of the drugs used to treat these disorders. Sex differences in the incidence and/or clinical course of these disorders and in the effectiveness of related dopaminergic and serotonergic drug therapies suggest that primate striatal indolamines and catecholamines are also influenced by gonadal hormones. However, while well studied in rats, relatively little is known about precisely how gonadal steroids modulate stratial dopamine and serotonin systems in primates. To begin to address this issue, the present studies explored the effects of ovarian steroids on the serotonergic and dopaminergic innervation densities of the caudate, putamen, and the nucleus accumbens in young adult rhesus monkeys. Using densitometry to quantify immunoreactivity for serotonin and for the catecholamine-synthesizing enzyme tyrosine hydroxylase, innervation densities were compared in identified, functionally specialized striatal subdomains across animals that were either ovariectomized or ovariectomized and supplemented with estradiol and/or progesterone, i.e. in a primate model of surgical menopause, with and without hormone replacement therapy. These analyses revealed clear examples of structure-, hemisphere-, and replacement regimen-specific effects of changes in circulating steroids on the densities of each afferent system examined. Further, the predominantly stimulatory effects observed occurred in striatal areas analogous to those suspected as sites of localized dopamine and/or serotonin compromise in Parkinson's disease and schizophrenia. Thus, the hormone actions identified in this study could hold relevance for some of the sex differences identified in relation to these disorders, including the findings of decreased incidence and/or symptom severity in women that have led to hypotheses of protective effects for estrogen.