EFFECT OF MUSCIMOL ON HALOPERIDOL-INDUCED ALTERATION OF NEUROTENSIN GENE-EXPRESSION IN THE STRIATUM AND NUCLEUS-ACCUMBENS THE RAT

Acute neuroleptic administration increases the expression of neurotens in/neuromedin (NT/N) gene in rat dorsolateral striatum and shell secto r of the nucleus accumbens. The purpose of this study was to examine m odulation of neuroleptic induction of NT/N and the proto-oncogene c-fo s expression by the GABA, 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 S-35-antisense probe s. Muscimol alone had no measurable effect on basal levels of NT/N or c-fos mRNA in either the dorsolateral striatum or the nucleus accumben s. However, co-administration of muscimol with haloperidol reduced hal operidol-induced increases in NT/N as well as c-fos mRNA in the dorsol ateral striatum. In contrast, NT/N mRNA expression in accumbal shell i nduced by haloperidol was not modulated by co-administration of muscim ol. These data suggest that GABA, receptors may be involved in regulat ion of NT/N gene expression in the DLSt, but not in the nucleus accumb ens.