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This study illustrates how a 2 week, twice daily 7.5 mg\/kg d\u2010amphetamine or saline regimen alters rat brain regional expression of transcription factor genes, including <jats:italic>c fos<\/jats:italic>, fos\u2010B, jun\u2010B, <jats:italic>c jun<\/jats:italic>, and <jats:italic>zif<\/jats:italic>268, and seeks potential correlations between those changes and alterations in neurotransmitter levels and behavioral novelty responses.<\/jats:p><jats:p>Amphetamine withdrawal\u2010induced 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 \u201cstereotypy time\u201d 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.<\/jats:p><jats:p>Chronic saline injections are followed by a consistent decrease in transcription factor gene expression, observed 6 h after the last injection, followed by a \u201crebound\u201d increase at 12 h. These changes are accompanied by dramatic, mostly biphasic alterations in prefrontal cortical biogenic amines and by a short\u2010lived increase in striatal dopamine turnover. At the same time, rats display much longer\u2010lasting decreases in locomotor responses when exposed to a novel environment, with recovery occurring only 54 h after the last injection.<\/jats:p><jats:p>The delayed recovery of behavioral responses to novelty is consistent with potential involvement of changes in transcription factor\u2010mediated gene expression in neurochem\u2010 ical mechanisms underlying psychostimulant withdrawal and chronic injection stress\u2010 induced behavioral alterations. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.890190309","type":"journal-article","created":{"date-parts":[[2004,12,31]],"date-time":"2004-12-31T22:23:56Z","timestamp":1104531836000},"page":"212-227","source":"Crossref","is-referenced-by-count":50,"title":["Brain transcription factor gene expression, neurotransmitter levels, and novelty response behaviors: Alterations during rat amphetamine withdrawal and following chronic injection stress"],"prefix":"10.1002","volume":"19","author":[{"given":"Antonio M.","family":"Persico","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles W.","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Zaczek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Brannock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George R.","family":"Uhl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,12]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1523\/JNEUROSCI.07-09-02837.1987","article-title":"Single\u2010unit response of noradrenergic neurons in the locus coeruleus of freely moving cats I. 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