Age- and Sex-Related Characteristics of Tonic Gaba Currents in the Rat Substantia Nigra Pars Reticulata
Abstrakt
Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABA(A)ergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNRA) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the delta GABA(A) receptor (GABA(A)R) subunit and GABA(A)R mediated tonic currents.
We have used delta-specific immunochemistry and whole cell patch clamp to study GABA(A)R mediated tonic currents in the SNRA 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(A)R tonic current density, which correlated with the decline in delta subunit in the SNRA between PN15 and 30.
Furthermore, we show that the GABA(A)R tonic currents can be modified by muscimol (GABA(A)R agonist; partial GABA(C)R agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: alpha 4 beta 3 delta GABA(A)Rs agonist and GABA(C)R antagonist), and zolpidem (alpha 1-subunit selective GABA(A)R agonist) in age- and sex-dependent manner specific for each drug. We propose that the emergence of the GABA(A)R-sensitive anticonvulsant effects of the rat SNRA during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNRA neurons, although other sex-specific factors are also involved.