Abstract

Previous experiments have shown that enhanced glutamate neurotransmission in the ventromedial hypothalamus by administration of glutamate or its selective receptor agonists kainate, N-methyl-D-aspartic acid or Ü-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA), results in a pronounced inhibition of proceptive and consummatory sexual behaviors. The five chapters encompassing this thesis were designed to expand our comprehension of the role that ventromedial hypothalamic glutamate plays in the control of sexual behavior in the female rat. The experiment presented in Chapter 1 shows that a substantial proportion of the neurons activated in the ventromedial hypothalamus by vaginocervical stimulation are glutamatergic, and that priming with estradiol benzoate and progesterone inhibits this activation. Chapter 2 investigated the effect of 6,7-Dinitroquinoxaline-2,3-dione (DNQX), a glutamate antagonist, on estrus termination, when infused in the ventromedial hypothalamus of female rats. DNQX effectively reversed the effect of vaginocervical stimulation on appetitive behaviors, lordosis quotient and lordosis magnitude, but had no effect on pacing, defensive behaviors, or male ejaculations. These results suggest that blocking glutamate transmission at the AMPA/kainate receptor delays onset of estrus termination. The experiment presented in Chapter 3 analyzed the pattern of glutamate release in the ventromedial hypothalamus during a 2-hour copulation session with a sexually vigorous male following priming with oil, estradiol benzoate or extradiol benzoate and progesterone. The results suggest that glutamate release patterns vary as a function of hormonal priming as well as stimulation received from being in proximity of a sexually mature male. Chapter 4 tested the hypothesis that glutamate release may be subject to regulation by Þ-aminobutryic acid (GABA), a neurotransmitter with cellular inhibitory properties and facilitative effects on lordosis upon infusion in the ventromedial hypothalamus. The results indicate that GABA A RÜ1 are upregulated by estradiol benzoate because the percentage of neurons that contained glutamate and expressed those receptors doubled when animals were primed with estradiol benzoate or estradiol benzoate and progesterone relative to oil. The experiment presented in Chapter 5 identified the medial preoptic area, anterior hypothalamic area, paraventricular nucleus, anterior hippocampus, and medial amygdala as the nuclei that send GABAergic projections to the ventromedial hypothalamus. These nuclei have previously been found to play important roles in the control of female sexual behavior. The function of ventromedial hypothalamic glutamate is explored in the general discussion.