Modulation of neuropeptide y and Y1 receptor expression in the amygdala by fluctuations in the brain content of neuroactive stereoids during ethanol withdrawal in mice

Increases on the content of neuroactive steroids induced by physiological or pharmacological conditions have been shown to results in increased expression of the gene encoding the Y1 receptor (Y1R) for neuropeptide Y in the medial amygdala of mice. With the use of Y1R/LacZ transgenic mice, which harbour the murine Y1R gene promoter linked to a LacZ reporter gene, we have now investigated the functional relations between fluctuations in the brain content of neuroactive steroids induced by chronic voluntary ethanol consumption or ethanol withdrawal and both the level of NPY immunoreactivity and Y1R/LacZ transgene expression in the amygdala. The voluntary consumption of consecutive solutions of 3,6,10 and 20% (v/v) ethanol over four weeks increased the cerebrocortical concentrations of the progesterone metabolite 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha, 5alpha – TH PROG), with this effect being no longer apparent 48 hours after ethanol withdrawal. Ethanol withdrawal resulted in a significant decrease in the level of NPY immunoreactivity and a concomitant increase in Y1R/LacZ transgene expression in both the medial and central amygdala whereas chronic ethanol intake had no effect on these parameters. Treatment with the 5 alpha- reductase inhibitor finasteride during the last week of ethanol consumption, which prevented the increase in the cerebrocortical concentration of 3alpha, 5alpha – TH PROG normally apparent after 4 weeks of ethanol intake, also prevented the changes in the NPY immunoreactivity and transgene expression induced by ethanol withdrawal. These data suggest that 3alpha, 5alpha – TH PROG may play an important role in the changes in NPY/Y1R signalling in the amygdala during ethanol withdrawal.