Cs. Woolley et Bs. Mcewen, ESTRADIOL REGULATES HIPPOCAMPAL DENDRITIC SPINE DENSITY VIA AN N-METHYL-D-ASPARTATE RECEPTOR-DEPENDENT MECHANISM, The Journal of neuroscience, 14(12), 1994, pp. 7680-7687
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.