9407305 Mann ABSTRACT Reproductive experience (pregnancy and lactation) has long- term effects on hormonal, behavioral and neurochemical endpoints in female mammals, including affecting litter size in hamsters, timing of reproductive events in miniature swine, salt intake in rat and maternal behavior in mice, rats, gerbils, squirrels, ewes, and monkeys. Interestingly, reproductive experience also alters the brain, demonstrating neural plasticity in the adult female mammal. So far, only the endogenous opioid system has been shown to be altered both behaviorally and physiologically by reproductive experience. The goal of this Research Planning Grant is to utilize in situ hybridization histochemistry (ISHH) to determine if there are permanent changes in brain opioid prohormone gene expression as a consequence of repeated reproductive experience. During the 18 months of the planning period the ISHH technique will be set up and tested. When the technique has been perfected research will start to determine the long-term effects of repeated reproductive states. The levels of message RNA of the opioid prohormone, proopiomelanocortin (POMC), will be examined during the estrous cycle and during pregnancy in the brain of female rats will undergo steroid regimens that mimic pregnancy to uncover the mechanism underlying this effect. To demonstrate that repeated pregnancies and lactations produce long-term, possibly permanent, changes in the brain of the adult mammal has important implications for the study of neural plasticity and reproductive neurobiology.