Stress responses which, when uncontrolled, can result in psychological and physiological dysfunction, are believed to involve interactions between the hypothalamus-pituitary- adrenal (HPA) axis and the hypothalamus-pituitary-gonadal (HPG) axis. The long term goals of this project are to understand the steroid-induced neurochemical mechanisms that regulate the expression of behaviors such as sexual receptivity and stress responses or pathological conditions such as seizures. The steroid hormones, progesterone and corticosterone, alter serotonergic activity in a number of brain regions. Progesterone effects on serotonin are linked to the control of female sexual behavior while corticosterone effects on serotonergic activity are implicated in the stress response. Preliminary results suggest progesterone and corticosterone act synergistically to markedly potentiate serotonin release in the central nucleus of the amygdala. The synergism between the two steroids on serotonin in the central nucleus of the amygdala may provide a mechanism for stress modification of female sexual receptivity. The proposed studies are designed to: 1) further characterize the synergistic steroid effects on serotonin release; 2) establish the potential physiological role of synergistic steroids effects on serotonin release in the central nucleus of the amygdala; and 3) explore the possibility that the synergistic effects of progesterone and corticosterone on serotonin release may be mediated through effects of the steroids on GABA. In addition, because of evidence linking steroid effects in the amygdala and seizure activity, studies will examine the relation between steroid enhanced serotonin release and seizure induction. The studies will be conducted in rats using in vivo micro dialysis to provide simultaneous evaluation of neurochemical and behavioral outcomes of steroid treatments and pharmacological interventions.
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