Induction of neurotensin and c-fos mRNA in distinct subregions of rat neostriatum after acute methamphetamine: Comparison with acute haloperidol effects

K. M. Merchant, G. R. Hanson, Daniel Dorsa

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Abstract

Large increases of neurotensin (NT)-like immunoreactivity in the rat neostriatum have been reported previously after treatment with either dopamine D2 receptor antagonists (e.g., haloperidol) or potent indirect dopamine agonists (e.g., methamphetamine). Combined administration of 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 methamphetamine. Our recent studies demonstrate that acute haloperidol treatment increases NT immunoreactivity in the striatum, at least in part, by enhancing the expression of the NT/neuromedin N (NT/N) gene in neurons confined to the dorsolateral sector of the striatum. Additionally, this induction of NT/N gene transcription in the dorsolateral striatum by haloperidol appears to involve participation of the immediate early gene, c-fos. The present study investigated alterations in NT/N and c-fos gene expression after acute methamphetamine (10 mg/kg s.c.) treatment and compared these changes to those observed after acute haloperidol (1 mg/kg i.p.) administration. Unlike haloperidol, methamphetamine increased NT/N mRNA expression in the periventricular dorsomedial quadrant of the striatum and induced c-fos mRNA primarily in the medial aspects of the central core of the neostriatum. These data suggest that Fos may not act as a primary transcription factor in methamphetamine-induced NT/N gene expression in the dorsomedial striatum. The results also indicate that additive increases in striatal NT-like immunoreactivity after simultaneous treatment with haloperidol and methamphetamine may be due to induction of NT/N gene expression in distinct neostriatal neuronal populations.

Original languageEnglish (US)
Pages (from-to)806-812
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume269
Issue number2
StatePublished - 1994
Externally publishedYes

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Neostriatum
Neurotensin
Methamphetamine
Haloperidol
Messenger RNA
Corpus Striatum
neuromedin N
Gene Expression
fos Genes
Immediate-Early Genes
Dopamine Agonists
Genes
Transcription Factors
Neurons

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Induction of neurotensin and c-fos mRNA in distinct subregions of rat neostriatum after acute methamphetamine: Comparison with acute haloperidol effects",
abstract = "Large increases of neurotensin (NT)-like immunoreactivity in the rat neostriatum have been reported previously after treatment with either dopamine D2 receptor antagonists (e.g., haloperidol) or potent indirect dopamine agonists (e.g., methamphetamine). Combined administration of 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 methamphetamine. Our recent studies demonstrate that acute haloperidol treatment increases NT immunoreactivity in the striatum, at least in part, by enhancing the expression of the NT/neuromedin N (NT/N) gene in neurons confined to the dorsolateral sector of the striatum. Additionally, this induction of NT/N gene transcription in the dorsolateral striatum by haloperidol appears to involve participation of the immediate early gene, c-fos. The present study investigated alterations in NT/N and c-fos gene expression after acute methamphetamine (10 mg/kg s.c.) treatment and compared these changes to those observed after acute haloperidol (1 mg/kg i.p.) administration. Unlike haloperidol, methamphetamine increased NT/N mRNA expression in the periventricular dorsomedial quadrant of the striatum and induced c-fos mRNA primarily in the medial aspects of the central core of the neostriatum. These data suggest that Fos may not act as a primary transcription factor in methamphetamine-induced NT/N gene expression in the dorsomedial striatum. The results also indicate that additive increases in striatal NT-like immunoreactivity after simultaneous treatment with haloperidol and methamphetamine may be due to induction of NT/N gene expression in distinct neostriatal neuronal populations.",
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T1 - Induction of neurotensin and c-fos mRNA in distinct subregions of rat neostriatum after acute methamphetamine

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AU - Hanson, G. R.

AU - Dorsa, Daniel

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