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 previously been shown to inhibit the release of proopiomelanocortin (POMC)-related peptides from the hypothalamus and to decrease mRNA levels in POMC neurons in the arcuate nucleus. To learn more about the precise role of the GABAergic system in POMC neuron regulation, we studied the effects of the administration (2 days) of the GABA(A) receptor agonist muscimol 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. Similarly, muscimol treatment decreased the signal by 20%. The concomitant administration of the two GABA(A) receptor agonists resulted in a decrease (28%) of mRNA levels that was significantly more marked than that induced by pentobarbital or muscimol alone. The present results, together with previous data from our laboratory, indicate that different activators of the GABA(A) receptor complex, including barbiturates, can negatively regulate POMC neuronal activity in the rat arcuate nucleus.