The expression of sexual receptivity in the female rat is a dynamic process during which sensory cues are constantly integrated with hormonal and neurochemical signals to modulate the behavioral response. The steroid hormone requirements for sexual receptivity (lordosis behavior) in the female rat have been extensively documented, but the contribution of sensory inputs to female reproductive behavior is less well characterized. The objective of the current grant proposal is to test the hypothesis that stimulation of the vomeronasal organ (VNO) by pheromonal signals from conspecific male promotes the expression of lordosis behavior in the female rat. It is proposed that the accessory olfactory system, which consists of the VNO, the accessory olfactory bulb (AOB) and the medial amygdala (AME), processes pheromonal signals to the ventromedial nucleus of the hypothalamus (VMH) where they are integrated to facilitate lordosis. It is further hypothesized that luteinizing hormone releasing hormone (LHRH) influences lordosis behavior by modulating the neurochemical events in the accessory olfactory system and in the VMH. To test these hypotheses, three specific aims are proposed. The first is to characterize the VNO- activated neuronal circuit from the AOB to the VMH. The second is to identify the putative neurotransmitters associated with processing VNO- activated signals within the accessory olfactory system and the VMH. The third is to determine the involvement of LHRH in the accessory olfactory system and in the VMH. The proposed studies will be performed in the female rat. A variety of techniques will be used including immunohistochemical procedure for detection of c-fos, putative neurotransmitters and LHRH; combined immunohistochemical and tract tracing (retrograde) methods; electrolytic lesions; brain cannulation; extracellular recording; iontophoresis and behavioral analysis. VNO activation will be induced by exposing the female to male-soiled bedding or to pheromonal signals from the conspecific male during copulatory behavior. In behavioral experiments, lordosis responding will be used as an index of sexual receptivity and will be measured in the repetitive mating paradigm. The proposed studies integrate anatomic, physiologic and behavioral approaches to provide a description of the VNO-activated neuronal circuitry and neurotransmitters by which pheromonal signals modulate the output of the VMH. The studies will also provide a detailed understanding of how a sensory system can interact with LHRH at the level of a hormone-primed neural substrate to amplify the expression of lordosis behavior. More importantly, these studies may provide information relevant to our understanding of the cellular mechanisms underlying olfactory/endocrine abnormalities in neuropsychiatric illnesses such as Kallman's syndrome, Alzheimer's disease, and sexual dysfunction.
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