Neurochemical Analysis of Motivated Behavior

NON-TECHNICAL SUMMARY Principal Investigator: Meisel, R. Proposal Number: IBN-9723876 Neurochemical Analysis of Motivated Behavior The long-term goal of this project is to explore how chemical systems in the brain control motivated behavior. Among motivated behaviors, ingestive behaviors such as feeding and drinking have formed the focus of such studies. To develop general principles to explain the control of motivated behaviors, the results from studies on a variety of behaviors (e.g., reproductive behavior, aggression) are needed. To date, little is known about the neurochemistry of the motivational components of female mating behavior. We have pursued studies showing a link between the mesolimbic dopamine system and the control of the incentive (e.g., reward) properties of female mating behavior, using hamsters as our experimental model. The studies in this proposal are designed to further pursue this link between neural dopamine pathways and female sexual behavior in three specific ways. First, we intend to continue microdialysis studies demonstrating proximal relationships between female reproductive function and extracellular dopamine levels in the nucleus accumbens. We have demonstrated that experienced female hamsters show higher, and more sustained extracellular dopamine levels during interactions with males compared with inexperienced females. As sensitization of responsiveness is one property of dopamine neurons repeatedly activated with drugs, we will explicitly test whether this augmentation of nucleus accumbens dopamine levels in experienced female hamsters reflects a sensitized response of these neurons to stimuli received during mating encounters. This would be the first such demonstration of sensitization of dopamine neurons resulting from the expression of a naturalistic behavior. Our second goal is to provide a broader neurological perspective on the relationship be tween dopamine and female mating behavior. To date, the nucleus accumbens and dorsal striatum are the only brain regions in which in vivo measurements of dopamine during mating encounters have been taken. We intend to extend this analysis to other behaviorally-relevant dopaminergic terminal fields, such as the frontal cortex, medial preoptic area, and amygdala. In the context of these experiments we will determine the degree to which dopamine in each of these areas is related to the expression of female mating behavior or some other factor associated with social encounters. A key issue in the interpretation of these behavioral findings centers around the degree to which individual dopaminergic neurons project to multiple targets. That is, do similarities or differences in dopaminergic activity in each terminal field derive from the activity of the same or different dopamine neurons. This is an unresolved issue for any species, and we propose to determine quantitatively the degree to which individual dopamine neurons innervate multiple terminal fields. Together these studies will provide a framework for defining how functional dopaminergic pathways regulate different components of female reproductive behavior, providing a basis for developing generalizations of the role of dopamine in motivated behavior.