ESTRADIOL REGULATES HIPPOCAMPAL DENDRITIC SPINE DENSITY VIA AN N-METHYL-D-ASPARTATE RECEPTOR-DEPENDENT MECHANISM

In the adult female rat, the densities of dendritic spines and synapse s on hippocampal CA1 pyramidal cells are dependent upon the ovarian st eroid estradiol; moreover, spine and synapse density fluctuate natural ly as ovarian steroid levels vary across the estrous cycle. To determi ne whether the effects of estradiol on dendritic spine density require activation of specific neurotransmitter systems, we have treated anim als concurrently with estradiol and one of four selective neurotransmi tter receptor antagonists: MK 801, a noncompetitive NMDA receptor anta gonist; CGP 43487, a competitive NMDA receptor antagonist; NBQX, an AM PA receptor antagonist; or scopolamine, a muscarinic receptor antagoni st. Our results indicate that the effects of estradiol can be blocked by treatment with either of the NMDA receptor antagonists, but treatme nt with an AMPA or muscarinic receptor antagonist has no effect on spi ne density. Thus, we have concluded that estradiol exerts its effect o n hippocampal dendritic spine density via a mechanism requiring activa tion specifically of NMDA receptors.