Increased expression of the neuropeptide Y receptor Y(1) gene in the medial amygdala of transgenic mice induced by long-term treatment with progesterone or allopregnanolone.
The neurosteroid allopregnanolone, a reduced metabolite of progesterone, induces anxiolytic effects by enhancing GABA(A) 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 Y(1)R/LacZ transgenic mice, which harbour a fusion construct comprising the promoter of the mouse gene for the Y(1) receptor for NPY linked to the lacZ gene, we previously showed that long-term treatment with benzodiazepine receptor ligands modulates Y(1) receptor gene expression in the medial amygdala. We have now investigated the effects of prolonged treatment with progesterone or allopregnanolone on Y(1)R/LacZ transgene expression, as determined by quantitative histochemical analysis of beta-galactosidase activity. Progesterone increased both the cerebrocortical concentration of allopregnanolone and beta-galactosidase expression in the medial amygdala. Finasteride, a 5alpha-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 beta-galactosidase activity in the medial habenula. These data suggest that allopregnanolone regulates Y(1) receptor gene expression through modulation of GABA(A) receptor function, and they provide further support for a functional interaction between GABA and neuropeptide Y in the amygdala.
Ferrara
G
G
Dipartimento di Anatomia, Farmacologia e Medicina Legale, Sezione di Farmacologia, Università di Torino, Torino, Italy.
Serra
M
M
Zammaretti
F
F
Pisu
M G
MG
Panzica
G C
GC
Biggio
G
G
Eva
C
C
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D009994:Osmolar Concentration; D011280:Pregnanolone / Q000378:metabolism / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D013997:Time Factors
D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D011374:Progesterone; D011280:Pregnanolone