The role of GABA in the control of gonadotropin-releasing hormone (GnRH) secretion is still controversial. In order to investigate the role of the GABAergic system in the regulation of GnRH gene expression in the rat brain, we studied the effects of chronic administration (2 days) of the GABAA receptor agonist muscimol and the central-type barbiturate receptor agonist pentobarbital on GnRH mRNA levels measured by in situ hybridization. Treatment with pentobarbital produced a 24% decrease in the hybridization signal. Similarly, muscimol treatment decreased the signal by 28%. The concomitant administration of the two GABAA receptor agonists resulted in a decrease (37%) of mRNA levels which was significantly more marked than that induced by pentobarbital or muscimol alone. The present results, together with previous data, indicate that the administration of pentobarbital or muscimol can inhibit not only the release of GnRH but also the gene expression of the neuropeptide as evaluated by mRNA level measurements.