TY - JOUR
T1 - Brain transcription factor gene expression, neurotransmitter levels, and novelty response behaviors
T2 - Alterations during rat amphetamine withdrawal and following chronic injection stress
AU - Persico, A. M.
AU - Schindler, C. W.
AU - Zaczek, R.
AU - Brannock, M. T.
AU - Uhl, G. R.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - c-fos
KW - Depression
KW - Immediate-early genes
KW - Prefrontal cortex
KW - Psychostimulant
KW - Striatum
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U2 - 10.1002/syn.890190309
DO - 10.1002/syn.890190309
M3 - Article
C2 - 7784961
AN - SCOPUS:0028916108
VL - 19
SP - 212
EP - 227
JO - Synapse
JF - Synapse
SN - 0887-4476
IS - 3
ER -