Abstracts

RATIONALE: In vivo fluctuations in gonadal hormones modulate both physiological and pathological processes involving the hippocampus. To assess hormonal effects on a functional hippocampal circuit, extracellular CA1 field responses were compared in slices from intact male, intact female, orchidectomized male, and ovariectomized female rats. METHODS: In Experiment 1, voltage input/output curves for the excitatory postsynaptic potential (EPSP) were used to assess baseline excitability. In Experiment 2, the effects of in vitro application of estrogen (E), progesterone (P), and testosterone (T) on excitability of slices from gonadectomized animals were measured. The in vitro kindling (IVK) model of slice epileptogenesis was then used to compare sex differences in kindled responses, including afterdischarge (AD) production and spontaneous burst rates (SBR). RESULTS: As seen in earlier studies, significant sex differences were detected in EPSP amplitude, with males having greater levels of excitability than females. Gonadectomy significantly decreased EPSP amplitude in both sexes. In vitro application of both E and T significantly increased EPSP amplitude and SBRs to near intact levels, whereas P replacement reduced EPSP amplitude. Following IVK, intact males showed greater SBRs than intact females, also suggesting greater excitability. AD number did not differ between hormone groups. CONCLUSIONS: These results suggest (1) both E and T (perhaps via aromitization to E) have excitatory effects on baseline EPSP and kindled hippocampal responses and (2) P s inhibitory effects may contribute to its clinical usefulness as an adjunctive anticonvulsant therapy. (Support: RO1DA05932 & KO2DA00249 to MAW & EFA Fellowship to MDS.)