Chronic modulation of the GABA(A) receptor complex regulates Y-1 receptor gene expression in the medial amygdala of transgenic mice

NPY exerts anxiolytic effects, which are mediated by activation of Y-1 rece ptors in the amygdala. It has been shown that diazepam counteracts the anxi ogenic effect of Y-1 receptor antagonists, suggesting that NPYergic and GAB Aergic systems are coupled in the regulation of anxiety. We used a transgen ic mouse model, expressing a mouse Y-1 receptor-beta-galactosidase fusion g ene (Y1R/LacZ), to study the effect of positive or negative modulators of G ABA(A) receptors on Y-1 receptor gene expression. Mice were treated for 14 days with diazepam (4 or 20 mg/kg), the anxiolytic beta-carboline-derivativ e abecarnil (0.3 or 6 mg/kg) and the anxiogenic beta-carboline FG7142 (20 m g/kg). Transgene expression was determined by quantitative analysis of beta -galactosidase histochemical staining in the medial amygdala and in the med ial habenula as a control region. Chronic treatment with 20 mg/kg diazepam or 6 mg/kg abecarnil significantly increased, whereas FG7142 decreased, tra nsgene expression in the medial amygdala. A transient decrease in transgene expression was observed in the medial amygdala six hours after the acute t reatment with 20 mg/kg FG7142 but not with diazepam or abecarnil. No signif icant changes were observed in the medial habenula. These data suggest that modulation of GABA(A) receptor function may regulate Y-1 receptor gene exp ression in medial amygdala. (C) 2000 Elsevier Science Ltd. All rights reser ved.