INDUCTION OF NEUROTENSIN AND C-FOS MESSENGER-RNA IN DISTINCT SUBREGIONS OF RAT NEOSTRIATUM AFTER ACUTE METHAMPHETAMINE - COMPARISON WITH ACUTE HALOPERIDOL EFFECTS

Large increases of neurotensin (NT)-like immunoreactivity in the rat n eostriatum have been reported previously after treatment with either d opamine D-2 receptor antagonists (e.g., haloperidol) or potent indirec t dopamine agonists (e.g., methamphetamine). Combined administration o f these two opposite classes of drugs results in additive increases in striatal NT-like immunoreactivity suggesting that distinct mechanisms may underlie increases in NT content after haloperidol and methamphet amine. Our recent studies demonstrate that acute haloperidol treatment increases NT immunoreactivity in the striatum, at least in part, by e nhancing the expression of the NT/neuromedin N (NT/N) gene in neurons confined to the dorsolateral sector of the striatum. Additionally, thi s induction of NT/N gene transcription in the dorsolateral striatum by haloperidol appears to involve participation of the immediate early g ene, c-fos. The present study investigated alterations in NT/N and c-f os gene expression after acute methamphetamine (10 mg/kg s.c.) treatme nt and compared these changes to those observed after acute haloperido l(1 mg/kg i.p.) administration. Unlike haloperidol, methamphetamine in creased NT/N mRNA expression in the periventricular dorsomedial quadra nt of the striatum and induced c-fos mRNA primarily in the medial aspe cts of the central core of the neostriatum. These data suggest that Fo s may not act as a primary transcription factor in methamphetamine-ind uced NT/N gene expression in the dorsomedial striatum. The results als o indicate that additive increases in striatal NT-like immunoreactivit y after simultaneous treatment with haloperidol and methamphetamine ma y be due to induction of NT/N gene expression in distinct neostriatal neuronal populations.