PT  - JOURNAL ARTICLE
AU  - David R. Benavides
AU  - Jennifer J. Quinn
AU  - Ping Zhong
AU  - Ammar H. Hawasli
AU  - Ralph J. DiLeone
AU  - Janice W. Kansy
AU  - Peter Olausson
AU  - Zhen Yan
AU  - Jane R. Taylor
AU  - James A. Bibb
TI  - Cdk5 Modulates Cocaine Reward, Motivation, and Striatal Neuron Excitability
AID  - 10.1523/JNEUROSCI.4061-07.2007
DP  - 2007 Nov 21
TA  - The Journal of Neuroscience
PG  - 12967--12976
VI  - 27
IP  - 47
4099  - http://www.jneurosci.org/content/27/47/12967.short
4100  - http://www.jneurosci.org/content/27/47/12967.full
SO  - J. Neurosci.2007 Nov 21; 27
AB  - Cyclin-dependent kinase 5 (Cdk5) regulates dopamine neurotransmission and has been suggested to serve as a homeostatic target of chronic psychostimulant exposure. To study the role of Cdk5 in the modulation of the cellular and behavioral effects of psychoactive drugs of abuse, we developed Cre/loxP conditional knock-out systems that allow temporal and spatial control of Cdk5 expression in the adult brain. Here, we report the generation of Cdk5 conditional knock-out (cKO) mice using the αCaMKII promoter-driven Cre transgenic line (CaMKII-Cre). In this model system, loss of Cdk5 in the adult forebrain increased the psychomotor-activating effects of cocaine. Additionally, these CaMKII-Cre Cdk5 cKO mice show enhanced incentive motivation for food as assessed by instrumental responding on a progressive ratio schedule of reinforcement. Behavioral changes were accompanied by increased excitability of medium spiny neurons in the nucleus accumbens (NAc) in Cdk5 cKO mice. To study NAc-specific effects of Cdk5, another model system was used in which recombinant adeno-associated viruses expressing Cre recombinase caused restricted loss of Cdk5 in NAc neurons. Targeted knock-out of Cdk5 in the NAc facilitated cocaine-induced locomotor sensitization and conditioned place preference for cocaine. These results suggest that Cdk5 acts as a negative regulator of neuronal excitability in the NAc and that Cdk5 may govern the behavioral effects of cocaine and motivation for reinforcement.