期刊
JOURNAL OF NEUROCHEMISTRY
卷 118, 期 1, 页码 126-139出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1471-4159.2011.07281.x
关键词
glycogen synthase kinase 3 beta; locomotor activity; methamphetamine; nucleus accumbens; sensitization
资金
- National Basic Research Program of China [2009CB522000]
- Natural Science Foundation of China [81071079]
- Natural Science Foundation of Beijing Municipality [7091003, 7092058]
As a ubiquitous serine/threonine protein kinase, glycogen synthase kinase 3 beta (GSK-3 beta) has been considered to be important in the synaptic plasticity that underlies dopamine-related behaviors and diseases. We recently found that GSK-3 beta activity in the nucleus accumbens (NAc) core is critically involved in cocaine-induced behavioral sensitization. The present study further explored the association between the changes in GSK-3 beta activity in the NAc and the chronic administration of methamphetamine. We also examined whether blocking GSK-3 beta activity in the NAc could alter the initiation and expression of methamphetamine (1 mg/kg, i.p.)induced locomotor sensitization in rats using systemic administration of lithium chloride (LiCl, 100 mg/kg, i.p) and brain region-specific administration of the GSK-3 beta inhibitor SB216763 (1 ng/side). We found that GSK-3 beta activity increased in the NAc core, but not NAc shell, after chronic methamphetamine administration. The initiation and expression of methamphetamine-induced locomotor sensitization was attenuated by systemic administration of LiCl and direct infusion of SB216763 into the NAc core, but not NAc shell. These results indicate that GSK-3 beta activity in the NAc core mediates the initiation and expression of methamphetamine-induced locomotor sensitization, suggesting that GSK-3 beta may be a potential target for the treatment of psychostimulant addiction.
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