Sex steroid effects on extrahypothalamic CNS. I. Estrogen augments neuronal responsiveness to iontophoretically applied glutamate in the cerebellum

Abstract

The purpose of this study was to test whether 17β-estradiol (E 2) could alter neuronal activity or responsiveness to iontophoretically applied amino acid neurotransmitters in an area not reported to contain classical E 2 receptors. Such a region is the cerebellum, which was selected as a model system for these studies because it has been well characterized electrophysiologically. Extracellular activity of cerebellar Purkinje neurons was recorded from urethane-anesthetized, adult, ovariectomized rats using multibarrel glass micropipets. Spontaneous firing rate and responses of single units to microiontophoretic pulses (10 s pulses every 40 s) of GABA (10–50 nA) or glutamate (GLUT, 3–40 nA) were examined before, during and after iontophoretic (0.25 mM 17β-estradiol hemisuccinate) or jugular i.v. (100, 300 or 1000 ng/kg 17β-estradiol) administration of E 2. Both modes of E 2 administration resulted in a significant increase in Purkinje cell excitatory responses to GLUT, independent of the direction of change in spontaneous firing rate. This effect was seen as early as one minute after iontophoretic application of E 2 and 10–40 min following i.v. E 2. In all cases, recovery to the control level of response was not observed by 2 h following E 2 administration.17α-E 2 (300ng/kg) resulted in a less pronounced, transient increase in GLUT response, while a lower dose (100 ng/kg) did not have any effect. Prior administration of the anti-estrogen tamoxifen did not prevent any of the observed E 2 effects. In addition, estrogen-priming did not alter E 2-induced potentiation of GLUT responses. In contrast to the effect of E 2 on GLUT responsiveness, GABA-mediated inhibition of Purkinje cells was either increased, antagonized or unchanged following E 2 application. In summary, this study suggests the hypothesis that circulating levels of E 2 may alter neuronal sensitivity to specific neurotransmitter substances within the cerebellar circuitry.