The overall objectives of this proposal is to study the effect of hormones on brain catecholamine physiology. The accidental discovery that the responsiveness of striatal tissue in vitro to amphetamine-induced dopamine release is present only in orchidectomized (orchx) but not in ovariectomized (ovx) rats prompted the interest to examine further this problem. Preliminary results show that the responsiveness of striatal tissue in vitro to amphetamine-induced dopmine release 1) varies during the estrous cycle; 2) it can be reinstated in ovx rats by pretreatment with estradiol benzoate progesterone; and 3) it is always present in intact male rats, orchx or orchx - testosterone propionate treated animals. It is the intent of this proposal to examine in detail and in depth such a novel finding since it offers a new model to investigate the quest of how hormones affect brain catecholamine physiology. To this end both in vitro (a perifusion system) and in vivo (a push-pull cannulae) procedures to measure the release of dopamine (DA) and norepinephrine (NE) from two well defined neuroanatomical structures of the rat's brain rich in catecholamine terminals but markedly different in their functions, the mediobasal hypothalamus (MBH) and corpus striatum (CS) will be employed. The studies proposed will define the role of structure-specificity (MBH vs. CS), stimulus-specificity (K ion, acetylcholine and amphetamine), sex-dependency (male vs. female), hormonal-dependency (gonadal steroids and PRL) and development in the basal and stimulated release of catecholamine from specific areas of the brain. Moreover, the use of neuropharmacological and subcellular (synaptosomes) approaches will tend to clarify the mechanism(s) by which hormones modulate synaptic transmission. These analyses proposed in this project at three levels: whole animal, tissue and subcellular, will generate new insights into the role of hormones in brain function.