NEGATIVE REGULATION OF PROOPIOMELANOCORTIN GENE-EXPRESSION BY GABA(A)RECEPTOR ACTIVATION IN THE RAT ARCUATE NUCLEUS

Activation of the GABA(A)-benzodiazepine receptor complex has previous ly been shown to inhibit the release of proopiomelanocortin (POMC)-rel ated peptides from the hypothalamus and to decrease mRNA levels in POM C neurons in the arcuate nucleus. To learn more about the precise role of the GABAergic system in POMC neuron regulation, we studied the eff ects of the administration (2 days) of the GABA(A) receptor agonist mu scimol and the central-type barbiturate receptor agonist pentobarbital on POMC mRNA levels measured by in situ hybridization. Treatment with pentobarbital produced a 12% decrease in the hybridization signal. Si milarly, muscimol treatment decreased the signal by 20%. The concomita nt administration of the two GABA(A) receptor agonists resulted in a d ecrease (28%) of mRNA levels that was significantly more marked than t hat induced by pentobarbital or muscimol alone. The present results, t ogether with previous data from our laboratory, indicate that differen t activators of the GABA(A) receptor complex, including barbiturates, can negatively regulate POMC neuronal activity in the rat arcuate nucl eus.