Gonadectomy and sex modulate spontaneous activity of substantia nigra pars reticulata neurons without modifying GABA/benzodiazepine responsiveness

Abstract

Gonadal steroid hormones or their derivatives can alter the GABA receptor complex and GABA-mediated responses. This study examines the influences of the in vivo gonadal steroid milieu on neuronal responses to GABA and benzodiazepine agonists in the substantia nigra pars reticulata (SNr) of rats. Spontaneous activity and microiontophoretic sensitivity to GABA of single SNr neurons were analyzed in chloral hydrate anesthetized intact male, intact female, orchidectomized male, and ovariectomized female rats using extracellular electrophysiological techniques. Benzodiazepine responses in each hormone group were assessed as 1) the ability of the iontophoretically applied midazolam to enhance GABA sensitivity and 2) the ability of systemically administered diazepam to decrease SNr firing rate. The results indicate that neither sex nor castration modified GABA sensitivity or benzodiazepine responsiveness in the SNr. However, a heightened level of basal SNr activity was observed in males compared to orchidectomized, intact female, or ovariectomized rats. Elevated SNr activity was also observed in males compared with other hormone groups following iontophoretic application of the GABA antagonist SR95531, suggesting that this augmentation in firing rate may be independent of nigral GABAergic control. Regulation of in vivo spontaneous SNr activity may be associated with gonad-related influences on the nigrostriatal system, but appears unrelated to intrinsic alterations in GABA/benzodiazepine responses in this area.