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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.

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


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.

[Indexed for MEDLINE]

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