Effect of acute and chronic administration of methamphetamine on activator protein-1 binding activities in the rat brain regions.
The activator protein-1 (AP-1) binding activities in the three brain regions (striatum, nucleus accumbens, cingulate cortex) increased after a single methamphetamine (METH, 4 mg/kg) injection and reached maximum levels after 180 min. Pretreatment with SCH 23390 (0.5 mg/kg), a selective dopamine D1 receptor antagonist, significantly inhibited the enhanced AP-1 binding activities induced by acute METH (4 mg/kg) administration. In chronic experiments, rats were pretreated with METH (4 mg/kg) or saline for 14 days. The AP-1 binding activities after a 1-week abstinence from chronic administration of MAP increased significantly in all the brain regions compared with those of the saline-treated controls, whereas after a 4-week abstinence, the AP-1 binding activity decreased significantly in the cingulate cortex, but not striatum or nucleus accumbens, compared with the saline-treated control group. A METH challenge after a 4-week abstinence period induced significantly more intense stereotypy, but lower AP-1 binding activities in all the brain regions of rats treated with repeated METH than repeated saline injections. The super-shift assay revealed that after a 1- or 4-week abstinence, there was no significant difference between the Fos-related antigens (Fras) contents of the saline- and METH-treated groups in any brain region examined, and that the Jun family protein levels of the METH-treated group increased significantly in the striatum and nucleus accumbens after a 1-, but not 4-, week abstinence. These results suggest that chronic METH administration leads to delayed decay of the induced AP-1 binding activities and Jun component levels after abstinence for up to 1 week, but results in no change in or decreases these activities and attenuates METH challenge-induced AP-1 binding activities after abstinence for 4 weeks.
Akiyama
K
K
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Ishihara
T
T
Kashihara
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D001552:Benzazepines; D018808:Transcription Factor AP-1; D008694:Methamphetamine