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Brain transcription factor gene expression, neurotransmitter levels, and novelty response behaviors: Alterations during rat amphetamine withdrawal and following chronic injection stress
Author(s) -
Persico Antonio M.,
Schindler Charles W.,
Zaczek Robert,
Brannock Michael T.,
Uhl George R.
Publication year - 1995
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890190309
Subject(s) - dopamine , amphetamine , prefrontal cortex , striatum , neurotransmitter , gene expression , stereotypy , endocrinology , nucleus accumbens , transcription factor , medicine , psychology , neuroscience , pharmacology , chemistry , biology , gene , central nervous system , biochemistry , cognition
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 neurochem‐ ical mechanisms underlying psychostimulant withdrawal and chronic injection stress‐ induced behavioral alterations. © 1995 Wiley‐Liss, Inc.