The ventromedial nucleus of the hypothalamus (VMH) has been shown by our laboratory to be involved in the regulation of maternal behavior in rats. The VMH is part of a neural circuit in the brain that inhibits maternal behavior in virgin and first- time pregnant (primigravid) females. The experiments described in the present grant proposal will use behavioral and neurochemical approaches to identify the possible mechanisms of action of the VMH on the inhibition of maternal behavior. The hypothesis underlyingthe present proposal is that under normal physiological conditions the VMH inhibits the display of maternal behavior in virgin and primigravid rats by inhibiting the actions of the medial preoptic area (MPOA, an area crucially involved in the display of maternal behavior). The first specific aim is to determine whether the VMH is activated following pup exposure in primigravid and steroid-primed, virgin rats and whether activated neurons also contain progesterone receptors. Experiments 1 and 3 will use Fos immunohistochemistry (IHC) to determine if neurons in the VMH are activated in the presence of foster pups in primigravid and steroid-primed, virgin rats. Experiments 2 and 4 will determine if progesterone receptors are colocalized with the activated neurons following pup exposure in primigravid and steroid-primed, virgin rats. The second specific aim is to examine the involvement of neophobia in the onset of maternal behavior. Experiments 5 through 9 will use mainly behavioral methods to determine if progesterone antagonists and/or anxiplytic drugs will stimulate the onset of maternal behavior in primigravid and steroid-primed, virgin rats. Experiment 5 will determine if central administration of mifepristone will block the inhibition of maternal behavior in primigravid rats, while experiment 6 will use central mifepristone in combination with systemic fmasteride, a progesterone metabolism blocker, to determine the neural site of progesterone's action. Experiments 7 and 8 will determine if anxiolytic drugs, e.g., diazepam or flumazenil, will stimulate the onset of maternal behavior in primigravid and estrogen-treated primigravid rats. Experiment 9 will determine if anxiolytic drugs will stimulate maternal behavior in steroid-primed, virgin rats and their effect of Fos activation in the VMH. Together, these studies will help identify and understand the mechanism that subserves maternal behavior in adult rats. In addition, these studies will clarify the role of progesterone in the onset of maternal behavior and the role of anxiety in preventing the female from acting maternally. The onset of maternal behavior - provides a model that will contribute more broadly to an understanding of natural behavioral responses in rats and other mammals, including humans. And may help explain the role of steroid hormones in anxiety-like conditions.