Acute and long-term effects of 17beta-estradiol on G(i/o) coupled neurotransmitter receptor function in the female rat brain as assessed by agonist-stimulated [35S]GTPgammaS binding.

Estrogens exert effects on mood, mental state, memory and other central nervous system (CNS) functions by modulating neurotransmitter receptor systems in the brain. Studies were designed to investigate the effect of 17beta-estradiol (E(2)) on agonist-stimulated [35S]GTPgammaS binding in membranes to assess the first step in the intracellular signal transduction cascade in a functional assay following: (1) an acute, one-time bolus subcutaneous injection, or (2) 14-day continuous exposure by a slow-release pellet implanted subcutaneously. In rats treated with E(2) acutely, the maximal response produced by activation of serotonin(1A) (5-HT(1A)) receptors was decreased approximately 25% in the hippocampus, cortex, and amygdala. Similarly, acute E(2) administration desensitized 5-HT(1B) and GABA(B) receptors in hypothalamus and cerebellum, respectively, and cannabinoid receptors in hippocampus and cortex. Although the maximal responses were decreased, acute E(2) treatment did not alter the EC(50) of any of the aforementioned receptors. The incubation of membranes prepared from the cortex of ovariectomized (OVX) rats with E(2) (1 microM) in vitro did not alter 5-HT(1A) or cannabinoid receptor-mediated [35S]GTPgammaS binding. By contrast to acute treatment in vivo, 14-day E(2) administration to OVX rats did not alter the maximal responses produced by activation of 5-HT(1A), 5-HT(1B), GABA(B), or cannabinoid receptors in any of the brain regions examined. Thus, it is concluded that acute E(2) administration in vivo modulates multiple G(i/o) coupled receptors in various regions of the female rat brain. Because these effects are observed only in vivo, it is concluded that cytosolic, nuclear and/or extraneuronal factors are required.