Increased expression of the neuropeptide Y receptor Y1 gene in the medial amygdala of transgenic mice induced by long-term treatment with progesterone or allopregnanolone

Abstract

The neurosteroid allopregnanolone, a reduced metabolite of progesterone, induces anxiolytic effects by enhancing GABAA receptor function. Neuropeptide Y (NPY) and GABA are thought to interact functionally in the amygdala, and this interaction may be important in the regulation of anxiety. By using Y1R/LacZ transgenic mice, which harbour a fusion construct comprising the promoter of the mouse gene for the Y1 receptor for NPY linked to the lacZ gene, we previously showed that long-term treatment with benzodiazepine receptor ligands modulates Y1 receptor gene expression in the medial amygdala. We have now investigated the effects of prolonged treatment with progesterone or allopregnanolone on Y1R/LacZ transgene expression, as determined by quantitative histochemical analysis of β-galactosidase activity. Progesterone increased both the cerebrocortical concentration of allopregnanolone and β-galactosidase expression in the medial amygdala. Finasteride, a 5α-reductase inhibitor, prevented both of these effects. Long-term administration of allopregnanolone also increased both the cortical concentration of this neurosteroid and transgene expression in the medial amygdala. Treatment with neither progesterone nor allopregnanolone affected β-galactosidase activity in the medial habenula. These data suggest that allopregnanolone regulates Y1 receptor gene expression through modulation of GABAA receptor function, and they provide further support for a functional interaction between GABA and neuropeptide Y in the amygdala.