Enhancing effects of estrogen on inhibitory avoidance performance may be in part independent of intracellular estrogen receptors in the hippocampus

Estradiol (E-2) can have classical actions via intracellular estrogen receptors (ERs) in the dorsal hippocampus, as well as effects independent of ERs ('non-genomic' mechanisms). These experiments investigated whether E-2's cognitive enhancing effects in the inhibitory avoidance task require actions at ERs in the dorsal hippocampus. Ovariectomized (ovx) rats were administered E-2 (s.c. or to the dorsal hippocampus), an E-2 conjugate (E-2:BSA), or vehicle and/or an ER antagonist, tamoxifen (10 mg/kg s.c.) or ICI 182,780 (10 mug intrahippocampally), or vehicle for 2 days prior to training (Day 3) and testing (Day 4) in the inhibitory avoidance task. Exp 1: crossover latencies in the inhibitory avoidance task were significantly increased in ovx rats with s.c. E-2 silastic capsules or s.c. injections of 1000 or 10 mug E-2 compared to vehicle-administered rats. Exp 2: bilateral inserts of E-2 to the dorsal hippocampus significantly increased crossover latencies compared to vehicle. Exp 3: s.c. tamoxifen, the ER antagonist, did not block the increased crossover latencies produced by 10 mug E-2 s.c. (compared to vehicle). Exp 4: s.c. tamoxifen did not block the increased crossover latencies produced by intrahippocampal E-2 (compared to vehicle). Exp 5 : 10 182,780 was unable to attenuate the increased crossover latencies produced by intrahippocampal E-2 Exp 6: E,:BSA administered to the dorsal hippocampus significantly enhanced performance on the inhibitory avoidance task compared to control implants to the hippocampus. The ability of systemic and intrahippocampal E-2 to similarly enhance inhibitory avoidance performance suggests that actions of E-2 in the dorsal hippocampus are sufficient to enhance cognitive performance. Further, that neither tamoxifen nor 10 182,780 blocked E-2's enhancing effects on inhibitory avoidance and that E-2:BSA was able to enhance performance suggest that non-genomic mechanisms may in part mediate E-2'S cognitive enhancing performance in this task. (C) 2002 Elsevier Science B.V. All rights reserved.