Voluntary exercise alters GABAA receptor subunit and glutamic acid decarboxylase-67 gene expression in the rat forebrain

Abstract

Voluntary exercise improves stress coping and lowers anxiety. Because of the role of GABA in these processes, we investigated changes in the central GABAergic system in rats with free access to a running wheel for 4 weeks. The control animals had no access to a running wheel. Using insitu hybridisation histochemistry, we studied changes in gene expression of various GABA_A receptor subunits as well as the GABA-synthesising enzyme glutamic acid decarboxylase-67 (GAD67) in the forebrain. There were region-specific decreases in α2, β3 and γ2 subunit mRNA expression and region-specific increases in β1 subunit expression. The α5 and δ subunits, in the forebrain specifically associated with extrasynaptic GABA_A receptors in the hippocampus, showed differential increases in expression levels. Expression of GAD67 mRNA was increased in many forebrain regions including all hippocampal cell layers, peri-paraventricular nucleus, bed nucleus stria terminalis, nucleus accumbens core and motor cortex, suggesting that long-term voluntary exercise enhances forebrain GABA synthesis capacity but in a region-specific manner. Thus, regular performance of exercise results in extensive changes in the forebrain GABAergic system that may be implicated in the changes in stress sensitivity and emotionality observed in exercising subjects.