Age- and Sex-Related Characteristics of Tonic Gaba Currents in the Rat Substantia Nigra Pars Reticulata

O. Chudomel, H. Hasson, M. Bojar, Solomon L. Moshe, Aristea S. Galanopoulou

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABA<inf>A</inf>ergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNR<inf>A</inf>) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the δ GABA<inf>A</inf> receptor (GABA<inf>A</inf>R) subunit and GABA<inf>A</inf>R mediated tonic currents. We have used δ-specific immunochemistry and whole cell patch clamp to study GABA<inf>A</inf>R mediated tonic currents in the SNR<inf>A</inf> of male and female postnatal day (PN) PN5-9, PN11-16, and PN25-32 rats. We observed age-related decline, but no sex-specific changes, in bicuculline (BIM) sensitive GABA<inf>A</inf>R tonic current density, which correlated with the decline in δ subunit in the SNR<inf>A</inf> between PN15 and 30. Furthermore, we show that the GABA<inf>A</inf>R tonic currents can be modified by muscimol (GABA<inf>A</inf>R agonist; partial GABA<inf>C</inf>R agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: α4β3δ GABA<inf>A</inf>Rs agonist and GABA<inf>C</inf>R antagonist), and zolpidem (α1-subunit selective GABA<inf>A</inf>R agonist) in age- and sex-dependent manner specific for each drug. We propose that the emergence of the GABA<inf>A</inf>R-sensitive anticonvulsant effects of the rat SNR<inf>A</inf> during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNR<inf>A</inf> neurons, although other sex-specific factors are also involved.

Original languageEnglish (US)
Pages (from-to)747-757
Number of pages11
JournalNeurochemical Research
Volume40
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

GABA-A Receptors
Sex Characteristics
Rats
GABA-A Receptor Agonists
Muscimol
Bicuculline
Immunochemistry
Sex Factors
Clamping devices
Pharmaceutical Preparations
Anticonvulsants
Neurons
Pars Reticulata
Current density

Keywords

  • Development
  • GABA agonists
  • Patch clamp
  • Sex differences
  • Substantia nigra pars reticulata
  • Tonic inhibition

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

Cite this

Age- and Sex-Related Characteristics of Tonic Gaba Currents in the Rat Substantia Nigra Pars Reticulata. / Chudomel, O.; Hasson, H.; Bojar, M.; Moshe, Solomon L.; Galanopoulou, Aristea S.

In: Neurochemical Research, Vol. 40, No. 4, 01.04.2015, p. 747-757.

Research output: Contribution to journalArticle

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AU - Galanopoulou, Aristea S.

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