Heterogeneity of hippocampal GABAA receptors: Regulation by corticosterone

Miles Orchinik, Steven S. Carroll, Yi Huey Li, Bruce S. McEwen, Nancy G. Weiland

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Abstract

Chronic stressors produce changes in hippocampal neurochemistry, neuronal morphology, and hippocampal-dependent learning and memory processes. In rats, stress-induced changes in CA3 apical dendritic structure are mediated by corticosterone (CORT) acting, in part, on excitatory amino acid neurotransmission. CORT also alters GABA-mediated inhibitory neurotransmission, so the GABAA receptor system may also contribute to dendritic remodeling and other stress-related changes in hippocampal function. A previous study indicated that chronic CORT treatment produces complex changes in GABAA receptor subunit mRNA levels, so we hypothesized that CORT alters the pharmacological properties of hippocampal GABAA receptors. To test this, adult male rats were treated with CORT or vehicle pellets for 10 d, after which we quantified [35S]t-butylbicyclo-phosphorothionate ([35S]TBPS) and [3H]flunitrazepam binding to GABAA receptors using in vitro receptor autoradiography. Pharmacological properties of receptors were assessed by examining the allosteric regulation of binding at both sites by GABA and 5α-pregnane-3α,21-diol-20-one (THDOC), an endogenous anxiolytic steroid. We found striking regional differences in the modulation of [35S]TBPS binding, particularly between strata radiatum and strata oriens, suggesting a functional heterogeneity among hippocampal GABAA receptors even within the apical versus basal dendrites of pyramidal neurons. Furthermore, we found that CORT treatment decreased the negative modulation of hippocampal [35S]TBPS binding by both GABA and THDOC and increased the enhancement of [3H]flunitrazepam binding by GABA and THDOC in the dentate gyrus. Together, these data suggest that prolonged exposure to stress levels of corticosteroids may alter hippocampal inhibitory tone by regulating the pharmacological properties of GABAA receptors in discrete dendritic subfields.

Original languageEnglish (US)
Pages (from-to)330-339
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number1
StatePublished - Jan 1 2001

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Keywords

  • 5α-pregnane-3α,21-diol-20one
  • Chronic stress
  • Corticosterone
  • GABA receptors
  • Hippocampus
  • Neurosteroid
  • T estosterone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Orchinik, M., Carroll, S. S., Li, Y. H., McEwen, B. S., & Weiland, N. G. (2001). Heterogeneity of hippocampal GABAA receptors: Regulation by corticosterone. Journal of Neuroscience, 21(1), 330-339.