Acute neuroleptic administration increases the expression of neurotensin/neuromedin (NT/N) gene in rat dorsolateral striatum and shell sector of the nucleus accumbens. The purpose of this study was to examine modulation of neuroleptic induction of NT/N and the proto-oncogene c-fos expression by the GABAA agonist muscimol. Adult male Sprague-Dawley rats were treated with saline, haloperidol (1 mg/kg); muscimol (3.2 mg/kg); or haloperidol (1 mg/kg) plus muscimol (3.2 mg/kg). Animals were sacrificed 1 h after drug administration. Expression of NT/N and c-fos mRNA was examined by in situ hybridization using 35S-antisense probes. Muscimol alone had no measurable effect on basal levels of NT/N or c-fos mRNA in either the dorsolateral striatum or the nucleus accumbens. However, co-administration of muscimol with haloperidol reduced haloperidol-induced increases in NT/N as well as c-fos mRNA in the dorsolateral striatum. In contrast, NT/N mRNA expression in accumbal shell induced by haloperidol was not modulated by co-administration of muscimol. These data suggest that GABAA receptors may be involved in regulation of NT/N gene expression in the DLSt, but not in the nucleus accumbens.