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Brain Res Mol Brain Res. 1993 Oct;20(1-2):91-100.

Brain transcription factor expression: effects of acute and chronic amphetamine and injection stress.

Author information

1
Molecular Neurobiology Branch, Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.

Abstract

Amphetamine influences behaviors and the expression of transcription factor genes in the central nervous system (CNS). A single d-amphetamine dose (7.5 mg/kg, i.p.) enhances behavioral stereotypy and augments brain expression of c-fos, fos-B, fra-1, zif268, jun-B, and c-jun by 2-11 fold. When the single amphetamine dose is preceded by 28 saline injections over 14 days, it is half as effective in enhancing expression of these genes. Rats injected with 7.5 mg/kg i.p. twice daily for 2 weeks and sacrificed after the last injection reveal further attenuation or abolition of the amphetamine-induced mRNA upregulation. These stigmata of 'tolerance' in gene expression display partial overlap with behavioral tolerance, manifest as changes in locomotor activity. Rats receiving low (2 mg/kg) amphetamine challenge doses following the 2-week 7.5 mg/kg b.i.d. amphetamine treatment show tolerance to the locomotor activating effects of the drug; no tolerance is evident following a high (7.5 mg/kg) challenge dose. These data suggest that amphetamine-induced alterations in brain transcription factor gene expression can display 'tolerance' and possibly 'cross-tolerance' with the stress caused by i.p. injection.

PMID:
8255186
DOI:
10.1016/0169-328x(93)90113-4
[Indexed for MEDLINE]

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