GENES CONTROLLING LORDOSIS BEHAVIOR

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DESCRIPTION: This is a renewal of a project in its ninth year. The goal of this research is to understand the basic working circuit for producing lordosis behavior. The PI's previous work has yielded valuable information on the neural circuitry involved in controlling lordosis. The current work will extend this to an analysis of the molecular mechanisms controlling this behavioral response. The PI will focus this research on the role of oxytocin in mediating the lordosis response because a) it is a behaviorally relevant gene, b) oxytocin is found in brain areas shown to be part of the lordosis circuitry, and b) the genes for both the peptide (oxytocin) and its receptor are known. There are essentially two specific aims. The first is to examine the effectiveness of blocking the oxytocin gene on lordosis and to characterize this effect. The second aim is to do basically the same thing for the oxytocin receptor gene. The PI has preliminary data which provide support for the rationale and feasibility of the proposed experiments. The PI has shown, for example, that the facilitatory effect of oxytocin on lordosis is situated in the VMN, a site containing oxytocin receptors. He has also demonstrated that the excitatory action of oxytocin is mediated via oxytocin receptors. Using antisense oligo's for the oxytocin receptor the PI has found that lordosis is blocked when females are given estradiol (but not estrogen followed by progesterone). Finally, to show that the antisense technology works, he provides data from his laboratory showing that antisense oligo s for PR s reduce lordosis, and that PRir is reduced in VMN.