title: Activation of the GABA(A)-benzodiazepine receptor complex inhibits proopiomelanocortin gene expression in the rat arcuate nucleus.
abstract: Activation of the GABA(A)-benzodiazepine receptor complex has previously been shown to inhibit the release of alpha-melanocyte-stimulating hormone (alpha-MSH) from proopiomelanocortin (POMC) neurons of the hypothalamus. To examine whether long-term activation of the GABA(A) receptor may also modulate the expression of the POMC gene in hypothalamic neurons, we have investigated the effect of chronic treatment with the centraltype benzodiazepine receptor agonist clonazepam, alone or in combination with the GABA(A) receptor agonist muscimol, on POMC mRNA levels in four anatomical subdivisions of the arcuate nucleus of the rat hypothalamus, using quantitative in situ hybridization. Clonazepam treatment produced a significant decrease in POMC mRNA levels in all the regions of the arcuate nucleus with the exception of the most rostral one. Administration of both clonazepam and muscimol induced a marked reduction of mRNA levels in all the subdivisions of the arcuate nucleus. Chronic treatment with muscimol and clonazepam also induced a significant decrease in POMC mRNA level in the pars intermedia of the pituitary. These results, together with previous data, indicate that activation of the GABA(A)-benzodiazepine receptor complex inhibits the expression of the POMC gene as well as the release of POMC-derived mature peptides in both hypothalamic neurons and pituitary melanotrophs.
authors.affiliation: European Institute for Peptide Research, Laboratory of Molecular Endocrinology, CNRS URA 650, UA INSERM, University of Rouen, 76134 Mont-Saint-Aignan, France.
authors.forename: S
authors.initials: S
authors.lastname: Jegou
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
authors.forename: C
authors.initials: C
authors.lastname: Blasquez
authors.forename: G
authors.initials: G
authors.lastname: Pelletier
authors.forename: H
authors.initials: H
authors.lastname: Vaudry