Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor α2 subunit expression, and PKC ζ activity

被引:27
作者
Chen, Qiang
Lee, Tong H.
Wetsel, William C.
Sun, Qi-An
Liu, Yingmiao
Davidson, Colin
Xiong, Xueying
Ellinwood, Everett H.
Zhang, Xiuwu
机构
[1] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[5] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
关键词
GAD(65); GAD(67); GABA; PKC; cocaine; pergolide; ondansetron; nucleus accumbens; caudate; behavioral sensitization;
D O I
10.1016/j.bbrc.2007.03.041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have recently shown in rats that cocaine-induced behavioral sensitization can be reversed by a 5-day treatment with ondansetron given 3.5 h after daily pergolide injections. In this study we further investigated the molecular/neurochemical alterations underlying cocaine sensitization and pergolide/ondansetron-mediated reversal. Results revealed that glutamic acid decarboxylase (GAD(65)/ GAD(67)) is higher abundant in the nucleus accurribens (NAc) than that in the caudate and medial prefrontal cortex (mPFC), while GABA(A) receptor alpha 2 subunit level in the NAc shell is less abundant than that in the NAc core, mPFC and caudate. Cocaine sensitization led to (1) a decrease in GAD67 expression, an increase in total protein kinase C (PKC) xi subtype and phosphorylated PKC xi/lambda. levels in the NAc core; (2) a decrease in GAD67 and GABAA receptor a2 subunit expression, and an increase in phosphorylated PKC xi/lambda levels in the NAc shell; (3) an increase in GAD67 expression in the caudate. Importantly, pergolide/ondansetron treatment reversed these alterations. These results suggest that reversal of cocaine-induced behavioral sensitization is associated with reversal of region-specific changes in GABA function and PKC activity in the striatum. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:733 / 738
页数:6
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