Rapid effects of estrogens within the striatum with a possible role in female sexual behavior.

Abstract

Estradiol is known to influence gene expression through intracellular receptors. Interestingly, the adult rat striatum, which does not contain the estrogen receptor, also appears to be directly modulated by this steroid. The effects of estradiol within the striatum are often too rapid to be attributed to changes in genomic activation. To test the hypothesis that estradiol acts directly upon the striatum through a membrane receptor, estradiol was applied to striatal neurons while whole cell calcium currents were measured. Initial experiments identified several types of striatal calcium channels. Experiments examining the possibility that the striatum plays a role in paced copulation were also performed. Striatal neurons possess several types of high voltage activated calcium channels, separated by their sensitivity and resistance to nifedipine, $\omega$-AgTx-IVA, $\omega$-CgTx-GVIA, or $\omega$-Ctx-MVIIC. Application of estradiol to dissociated striatal neurons produced a reduction in whole cell calcium currents. The effect was typically occluded by nifedipine, suggesting L-type calcium channels were the predominant current inhibited by estradiol. The effect was sex- and steroid-specific. Estradiol conjugated to bovine serum albumen was also effective in reducing calcium currents, demonstrating estradiol was acting upon the membrane surface. Intracellular dialysis with GTP$\gamma$S significantly attenuated current recovery after steroid removal, suggesting estradiol acts through a G-protein coupled second messenger system. Upon verifying that estradiol alters striatal signaling, the purpose of the striatum being estrogen-dependent was posed. Female rats are known to regulate the interval between sexual contacts when able to remove themselves from male counterparts. The sensorimotor aspect of this "pacing" behavior could possibly be controlled by the striatum. It was found that estrogen- and progesterone-primed female rats displayed significant increases in extracellular concentrations of striatal dopamine during paced copulation. Female rats which were forced to copulate at the male rat's rate did not exhibit dopamine increases. Interestingly, non-receptive female rats primed only with estrogen exhibited increased concentrations of dopamine when presented with a male stimulus. On the other hand, oil treated animals showed no increase. The data suggest the female rat striatum is estrogen-sensitive and may play an important role in female sexual behavior.