Increased accumbens Cdk5 expression in rats after short-access to self-administered cocaine, but not after long-access sessions.

Upregulation of cyclin-dependent kinase 5 (Cdk5) after chronic cocaine administration has led to speculation that Cdk5 plays an important role in drug addiction. However, as Cdk5 involvement is implicated in a variety of neural events, including neuronal development, synaptic plasticity and learning, a specific role in drug abuse is yet to be determined. The present study utilized cocaine self-administration and food-reinforced operant procedures to assess possible relationships between cocaine intake, food-reinforced operant responding, behavioral activity, and Cdk5 levels in the nucleus accumbens (NAcc), ventral tegmental area (VTA), and prefrontal cortex (PFC) in rats. In Experiment 1, animals undergoing daily cocaine self-administration (1-h/30 days) or food-reinforced operant sessions (20-min/30 days) showed significant between-group differences in operant responding and behavioral activity, but no significant differences in NAcc, VTA or PFC Cdk5 levels compared to a Handled Control group. In Experiment 2, animals that had self-administered cocaine in 10 daily 1-h sessions (Short-Access Cocaine) showed significantly greater NAcc Cdk5 expression compared to an Unhandled Control group, and no evidence of cocaine-induced behavioral sensitization. Animals given 4-h daily access to cocaine over the same number of sessions (Long-Access Cocaine) showed significantly enhanced cocaine-reinforced responding and locomotor activation by the end of the sessions, but no significant differences in Cdk5 expression compared to Control animals. These findings suggest that overexpression of Cdk5 may be a transient adaptation to cocaine experience that subsides with increased cocaine exposure and does not correspond with measures of cocaine-induced behavioral sensitization.