The overall aim of this research is to understand the neurochemical bases of brain sexual dimorphism. In order to achieve this goal it is useful to select: (a) neurotransmitters which are likely to be involved in the control of gender-specific neural events; (b) brain regions involved in regulating these events; (c) hormonal treatments known to product different behavioral and/or neurochemical processes in adult males and females; (d) a species in which sexually dimorphic responses can be reversed by appropriate neonatal hormonal manipulations; and (e) research methods suitable to detect sexual dimorphisms in the regulation of neurotransmission. Preliminary data from this and other laboratories provide evidence implicating gonadal steroid hormones in the control of GABA and glutamate transmission in central nervous system (CNS) regions which govern reproductive physiology and behavior. Therefore, experiments described in this application propose to elucidate and for GABA and glutamate release in males and females.
This aim will be realized by studying glutamic acid decarboxylase (GAD) activity in microdissected brain regions and the in vitro release of GABA and glutamate from synaptosomes (nerve endings) isolated from specific regions of the hypothalamus (HYP) and preoptic area (POA) of adult rats. These brain regions play the most important role in the regulation of both sexually dimorphic hormone secretion and sexually dimorphic reproductive behaviors. Specific questions to be addressed include the following: (1) Are there sex differences in GAD activity or in basal or depolarization-evoked release of GABA and glutamate? (2) Are there sex differences in the regulation of GAD activity or of basal or depolarization-evoked GABA and glutamate release by ovarian steroid hormones? (3) Are there sex differences in norepinephrine modulation of basal or depolarization-evoked GABA and glutamate release? (4) Is neonatal exposure of the developing brain to testicular steroids responsible for inducing sexual dimorphisms in the adult regulation of GABA synthesis and/or GABA and glutamate release? (5) Are the developmentally based sex differences in ovarian steroid regulation of GABA and/or glutamate transmission correlated with sex differences in ovarian steroid induction of female reproductive behavior?
| Fleischmann, A; Makman, M H; Etgen, A M (1995) GABAA receptor activation induces GABA and glutamate release from preoptic area. Life Sci 56:1665-78 |
| Fleischmann, A; Etgen, A M; Makman, M H (1992) Estradiol plus progesterone promote glutamate-induced release of gamma-aminobutyric acid from preoptic area synaptosomes. Neuropharmacology 31:799-807 |
| Fleischmann, A; Makman, M H; Etgen, A M (1992) Characterization of glutamate efflux from preoptic area synaptosomes. Neuropharmacology 31:1171-8 |
