Scholars@Duke publication: Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor alpha2 subunit expression, and PKC zeta activity.

Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor alpha2 subunit expression, and PKC zeta activity.

Publication , Journal Article

Chen, Q; Lee, TH; Wetsel, WC; Sun, Q-A; Liu, Y; Davidson, C; Xiong, X; Ellinwood, EH; Zhang, X

Published in: Biochem Biophys Res Commun

May 11, 2007

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 accumbens (NAc) than that in the caudate and medial prefrontal cortex (mPFC), while GABA(A) receptor alpha2 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 GAD(67) expression, an increase in total protein kinase C (PKC) zeta subtype and phosphorylated PKC zeta/lambda levels in the NAc core; (2) a decrease in GAD(67) and GABA(A) receptor alpha2 subunit expression, and an increase in phosphorylated PKC zeta/lambda levels in the NAc shell; (3) an increase in GAD(67) 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.

Duke Scholars

Author William Christopher Wetsel Psychiatry & Behavioral Sciences, Behavioral Medicine & Neur ...

Published In

Biochem Biophys Res Commun

DOI

10.1016/j.bbrc.2007.03.041

ISSN

0006-291X

Publication Date

May 11, 2007

Volume

356

Issue

Start / End Page

733 / 738

Location

United States

Related Subject Headings

Stereotyped Behavior
Receptors, GABA-A
Rats, Sprague-Dawley
Rats
Protein Kinase C
Prefrontal Cortex
Pergolide
Ondansetron
Nucleus Accumbens
Male

Citation

APA

Chicago

ICMJE

MLA

NLM

Chen, Q., Lee, T. H., Wetsel, W. C., Sun, Q.-A., Liu, Y., Davidson, C., … Zhang, X. (2007). Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor alpha2 subunit expression, and PKC zeta activity. Biochem Biophys Res Commun, 356(3), 733–738. https://doi.org/10.1016/j.bbrc.2007.03.041

Chen, Qiang, Tong H. Lee, William C. Wetsel, Qi-An Sun, Yingmiao Liu, Colin Davidson, Xueying Xiong, Everett H. Ellinwood, and Xiuwu Zhang. “Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor alpha2 subunit expression, and PKC zeta activity.” Biochem Biophys Res Commun 356, no. 3 (May 11, 2007): 733–38. https://doi.org/10.1016/j.bbrc.2007.03.041.

Chen Q, Lee TH, Wetsel WC, Sun Q-A, Liu Y, Davidson C, et al. Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor alpha2 subunit expression, and PKC zeta activity. Biochem Biophys Res Commun. 2007 May 11;356(3):733–8.

Chen, Qiang, et al. “Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor alpha2 subunit expression, and PKC zeta activity.” Biochem Biophys Res Commun, vol. 356, no. 3, May 2007, pp. 733–38. Pubmed, doi:10.1016/j.bbrc.2007.03.041.

Chen Q, Lee TH, Wetsel WC, Sun Q-A, Liu Y, Davidson C, Xiong X, Ellinwood EH, Zhang X. Reversal of cocaine sensitization-induced behavioral sensitization normalizes GAD67 and GABAA receptor alpha2 subunit expression, and PKC zeta activity. Biochem Biophys Res Commun. 2007 May 11;356(3):733–738.