Chronic modulation of the GABA(A) receptor complex regulates Y1 receptor gene expression in the medial amygdala of transgenic mice.
NPY exerts anxiolytic effects, which are mediated by activation of Y1 receptors in the amygdala. It has been shown that diazepam counteracts the anxiogenic effect of Y1 receptor antagonists, suggesting that NPYergic and GABAergic systems are coupled in the regulation of anxiety. We used a transgenic mouse model, expressing a mouse Y1 receptor-beta-galactosidase fusion gene (Y1R/LacZ), to study the effect of positive or negative modulators of GABA(A) receptors on Y1 receptor gene expression. Mice were treated for 14 days with diazepam (4 or 20 mg/kg), the anxiolytic beta-carboline-derivative abecarnil (0.3 or 6 mg/kg) and the anxiogenic beta-carboline FG7142 (20 mg/kg). Transgene expression was determined by quantitative analysis of beta-galactosidase histochemical staining in the medial amygdala and in the medial habenula as a control region. Chronic treatment with 20 mg/kg diazepam or 6 mg/kg abecarnil significantly increased, whereas FG 7142 decreased, transgene expression in the medial amygdala. A transient decrease in transgene expression was observed in the medial amygdala six hours after the acute treatment with 20 mg/kg FG 7142 but not with diazepam or abecarnil. No significant changes were observed in the medial habenula. These data suggest that modulation of GABA(A) receptor function may regulate Y1 receptor gene expression in medial amygdala.
Oberto
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A
Sezione di Farmacologia, Dipartimento di Anatomia, Farmacologia e Medicina Legale, Università di Torino Italy.
Panzica
G
G
Altruda
F
F
Eva
C
C
D000494:Allosteric Regulation; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics*
D014151:Anti-Anxiety Agents; D002243:Carbolines; D018757:GABA Modulators; D011963:Receptors, GABA-A; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C062769:abecarnil; D003975:Diazepam