Reversal of cocaine sensitization-associated changes in GAD67 and GABAA receptor α2 subunit expression, and PKC ζ activity

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 GAD65 and GAD67 are higher abundant in the NAc than that in the caudate and mPFC, while GABAA receptor α2 subunit level in the NAc shell is less abundant than that in the NAc core, mPFC and caudate. Cocaine sensitization leaded to 1) decrease in GAD67 expression, increase in total PKC ζ and phosphorylated PKC ζ/λ levels in the NAc core; 2) decrease in GAD67 and GABAA receptor α2 subunit expression, and increase in phosphorylated PKC ζ/λ levels in the NAc shell; 3) 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.

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