The objective of this project is to understand the interactions between gonadal steroids and monoamine neurotransmitters in brain tissue. Relatively simple and stereotyped behavioral patterns (e.g. lordosis in guinea pigs) that are known to be affected in predictable ways by the steroids estradiol and progesterone and by noradrenergic and serotonergic transmission, are used as indicators of steroid-transmitter interactions in particular brain regions. To pursue this objective the following specific aims are proposed: 1) Establish that norepinephrine facilitates steroid-dependent lordosis by acting on Alpha1-adrenoceptors. Attempt to show that noradrenergic action on Alpha1-adrenoceptors influences lordosis in mature females by regulating the concentration of estrogen and/or progestin receptors in particular brain regions or discrete nuclei. The important implication of this work is that certain types of neural activity selectively and acutely alter brain sensitivity to steroids. 2) Describe the ontogeny of noradrenergic transmission through Alpha-receptors (a system that facilitates steroid-dependent lordosis). Attempt to understand mechanisms of regulation of Alpha-adrenoceptors by studying a neuroblastoma cell line. 3) Trace the ontogeny of serotonin transimission (which inhibits steroid-dependent lordosis behavior). These analyses should give the most complete picture avilable of how steroids form behaviorally relevant interactive relationships with a monoamine transmitter that facilitates lordosis (norepinephrine) and a monoamine transmitter that inhibits lordosis (serotonin) in mature females. The unraveling of these processes may provide insights into the biological roots of steroid-sensitive complex behaviors and mood states in humans.
