Dopamine and GABAA receptor imbalance after ovariectomy in rats: model of menopause.

Abstract

A peak of first episodes of schizophrenia can occur in postmenopausal women. Furthermore, tardive dyskinesia is more common in postmenopausal women than in men of comparable age. This study investigated the effect of ovariectomy (2 weeks or 3 months) in rats as a model of decreased gonadal function associated with menopause. After ovariectomy, frontal cortex D1 receptors progressively decreased in density with no change of affinity over time. Striatal D1 and D2 receptors also had decreased density after ovariectomy with no change of affinity. In the substantia nigra pars reticulata, a progressive increase in [3H]flunitrazepam-specific binding associated with GABAA receptors was observed as a function of time following ovariectomy. It is hypothesized that low prefrontal cortex dopamine activity has implications in negative symptoms of schizophrenia and, furthermore, that GABAergic overactivity in the internal globus pallidus-substantia nigra pars reticulata complex plays a role in tardive dyskinesia. The present results suggest that, by reducing brain dopamine receptors and increasing GABAA receptors, gonadal hormone withdrawal may predispose to schizophrenia and dyskinesia.