TY - JOUR
T1 - Brain transcription factor expression
T2 - effects of acute and chronic amphetamine and injection stress
AU - Persico, Antonio M.
AU - Schindler, Charles W.
AU - O'Hara, Bruce F.
AU - Brannock, Michael T.
AU - Uhl, George R.
PY - 1993/10
Y1 - 1993/10
N2 - 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 sterotypy and augments brain expression of c-fos, fos-B, fra-1, zif 268, jun-B, and c-jun by 2-11 fold. When the single amphetamine dose is preceeded 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.
AB - 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 sterotypy and augments brain expression of c-fos, fos-B, fra-1, zif 268, jun-B, and c-jun by 2-11 fold. When the single amphetamine dose is preceeded 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.
KW - Amphetamine
KW - C-fos
KW - Immediate-early gene
KW - Sensitization
KW - Stress
KW - Tolerance
KW - Transcription factor
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U2 - 10.1016/0169-328X(93)90113-4
DO - 10.1016/0169-328X(93)90113-4
M3 - Article
C2 - 8255186
AN - SCOPUS:0027202079
SN - 0169-328X
VL - 20
SP - 91
EP - 100
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1-2
ER -