The proposed studies will test the hypotheses that somatodendritic 5-HT1A receptor function is modulated during the female estrous cycle, is different in male and female rats, and is modulated by estrogen. The somatodentric serotonin 1A (5-HT1A) autoreceptor of serotonin neurons has been targeted as a possible contributor to gender differences in central nervous system serotonergic function. Human females are the major consumers of antidepressant and antianxiety drugs, but most research with animal models has been performed in males. Recent evidence suggests that the human female's enhanced vulnerability to various mood disorders could reside in gender- and/or reproductive cycle-specific modulation of neurotransmitter systems that underlie these mood dysfunctions. The proposed experiments are designed to address the hypothesis that the proestrus female rat and the estrogen-treated ovariectomized rat have a reduced sensitivity to somatodendritic 5-HT1A autoreceptor activation. Males will be included in these studies in order to evaluate the putative gender difference in this receptor's function. Included in the experiments are: (a) a measurement of the release of 5-HT as estimated by microdialysis procedures in male and female rats and in ovariectomized rats, treated with estradiol benzoate, and (b) evaluation of the effects of the 5-HT1A somatodendritic receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), on 5-HT release. The somatodendritic 5-HT1A receptor is believed to be a common site of action for several antidepressant and antianxiety drugs. Consequently, an understanding of the gender, estrous cycle, and hormonal modulation of this receptor could have significance to the eventual identity of the mechanisms responsible for the human female's enhanced vulnerability to mood disorders.
