Brain transcription factor gene expression, neurotransmitter levels, and novelty response behaviors: Alterations during rat amphetamine withdrawal and following chronic injection stress

A. M. Persico, C. W. Schindler, R. Zaczek, M. T. Brannock, G. R. Uhl

Research output: Contribution to journalArticle

Abstract

Transcription factors are known to act as gene expression regulators, possibly linking extracellular stimuli to long-term modifications at the neuronal level. Such modifications may potentially underlie chronic psychostimulant- and stress-induced behavioral alterations. This study illustrates how a 2 week, twice daily 7.5 mg/kg d-amphetamine or saline regimen alters rat brain regional expression of transcription factor genes, including c-fos, fos-B, jun-B, c-jun, and zif 268, and seeks potential correlations between those changes and alterations in neurotransmitter levels and behavioral novelty responses. Amphetamine withdrawal-induced decreases in transcription factor mRNA levels, assessed using Northern blot analysis, appear most prominent in prefrontal cortex, begin approximately 12 h after the last injection, and largely recover to control levels by 54 h. Prefrontal cortical and striatal dopamine content, assessed using HPLC, decrease and recover over a similar time course. Behavioral 'stereotypy time' manifest by animals exposed to a novel environment, a measure sensitive to psychostimulant withdrawal, also decreases beginning 12 h after the last injection, is still significantly reduced at 54 h, and recovers at 72 h. Chronic saline injections are followed by a consistent decrease in transcription factor gene expression, observed 6 h after the last injection, followed by a 'rebound' increase at 12 h. These changes are accompanied by dramatic, mostly biphasic alterations in prefrontal cortical biogenic amines and by a short-lived increase in striatal dopamine turnover. At the same time, rats display much longer-lasting decreases in locomotor responses when exposed to a novel environment, with recovery occurring only 54 h after the last injection. The delayed recovery of behavioral responses to novelty is consistent with potential involvement of changes in transcription factor- mediated gene expression in neurochemical mechanisms underlying psychostimulant withdrawal and chronic injection stress-induced behavioral alterations.

Original languageEnglish
Pages (from-to)212-227
Number of pages16
JournalSynapse
Volume19
Issue number3
DOIs
Publication statusPublished - 1995

Keywords

  • c-fos
  • Depression
  • Immediate-early genes
  • Prefrontal cortex
  • Psychostimulant
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

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