Decreased calcineurin and increased phosphothreonine-DARPP-32 in the striatum of rats behaviorally sensitized to methamphetamine.
We investigated changes in signal transduction via calcineurin (CaN) in the striatum of rats behaviorally sensitized to methamphetamine (Meth). The rats were injected with Meth (4 mg/kg, s.c.) five times a week for 3 weeks and then were given a challenge dose of Meth (2 mg/kg, s.c.). Seven days after the challenge test, we determined the levels of CaN Aalpha and Abeta by Western blotting. We further immunoquantified DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, mw 32,000) and phosphothreonine-DARPP-32, which can be dephosphorylated at threonine sites by CaN. We found that both CaN Aalpha and Abeta were significantly decreased in the particulate fractions but were not changed in the soluble fractions from the striatum of Meth-sensitized rats as compared with control rats. The same findings were observed in the striatum of rats 6 h after the injection of PCP (10 mg/kg, s.c.). In the striatum of Meth-sensitized rats, phosphothreonine-DARPP-32 immunoreactivities significantly increased, but DARPP-32 immunoreactivities were not significantly different from those of the control rats. These results indicate that the activity of signal transduction via CaN is functionally decreased in the striatum of Meth-sensitized rats.
Lin
Xian-Hao
XH
Department of Psychiatry and Neurology, Kobe University School of Medicine, 650-0017, Japan.
Hashimoto
Takeshi
T
Kitamura
Noboru
N
Murakami
Naoya
N
Shirakawa
Osamu
O
Maeda
Kiyoshi
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D019703:Calcineurin / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors / Q000378:metabolism; D007202:Indicators and Reagents / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D010769:Phosphothreonine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D010769:Phosphothreonine; D008694:Methamphetamine; D019703:Calcineurin