Inhibition of Cdk5 in the nucleus accumbens enhances the locomotor-activating and incentive-motivational effects of cocaine.

ABSTRACT: Neuronal adaptations in striatal dopamine signaling have been implicated in enhanced responses to addictive drugs. Cyclin-dependent kinase 5 (Cdk5) regulates striatal dopamine signaling and is a downstream target gene of the transcription factor DeltaFosB, which accumulates in striatal neurons after chronic cocaine exposure. Here we investigated the role of Cdk5 activity in the nucleus accumbens (NAc) on cocaine-induced locomotor sensitization, responding for reward-associated stimuli (conditioned reinforcement), and cocaine self-administration under a progressive ratio schedule. Repeated infusions of the Cdk5 inhibitor roscovitine into the NAc before cocaine injections augmented both the development and expression of cocaine sensitization without having any intrinsic stimulant actions of

SUBMITTER: Taylor JR 

PROVIDER: S-EPMC1820723 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature