TY - JOUR T1 - A Role for Kalirin in the Response of Rat Medium Spiny Neurons to Cocaine JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.112.080044 SP - mol.112.080044 AU - Xinming Ma AU - Jianping Huang AU - Xiaonan Xin AU - Yan Yan AU - Richard E Mains AU - Betty A Eipper Y1 - 2012/07/24 UR - http://molpharm.aspetjournals.org/content/early/2012/07/24/mol.112.080044.abstract N2 - Kalirin 7 (Kal7), the major Kalirin isoform in adult brain, plays a key role in the formation of dendritic spines in hippocampal/cortical neurons. Its role in the GABAergic medium spiny neurons (MSNs) of the nucleus accumbens (NAc) and striatum, the areas known to play a key role in the common reward pathway, is not as well understood. Although Kal7 expression in mouse NAc increased in response to cocaine, MSN dendritic spine density did not differ from wildtype in Kal7 null mice. Unlike wildtype mice, Kal7 null mice did not respond to cocaine with an increase in MSN dendritic spine density. To explore further the role of Kal7 in cocaine-induced alterations in MSN morphology, we turned to the rat. Based on immunostaining, both Kal7 and Kal12 are expressed at moderate levels in the MSNs of the NAc and striatum. Expression of Kal7 and Kal12 in MSNs of both areas increases after repeated cocaine treatments. Over-expression of Kal7 in cultured MSN neurons increases dendritic spine density, as observed in rats after chronic cocaine administration. Reducing endogenous expression of all major Kalirin isoforms in cultured MSN neurons causes a decrease in total dendritic length and dendritic spine density. These data suggest that Kalirin is essential for maintaining spine density in NAc MSNs under normal conditions, and that Kal7 is an obligatory intermediate in the response of MSNs to repeated exposure to cocaine. ER -