Chronic Stress and Extended Access to Cocaine Produce Increased Drug Intake : : Involvement of [Kappa]-opioid Receptor Activation

The transition from recreational cocaine use to drug addiction (aka "drug dependence") is thought to be a result of the dysregulation of brain reward and stress systems. The present studies examined the participation of κ-opioid receptor activation in the escalation of cocaine intake produced by either extended-access to cocaine or stress. Part 1 : Dynorphin is a neuropeptide that activates κ-opioid receptors to produce negative emotional states (e.g., dysphoria) associated with cocaine dependence. Injection of norbinaltorphimine (norBNI), a [Kappa]-receptor antagonist, attenuated cocaine intake in rats allowed extended access (6 h/day). These findings indicate a functional role of [Kappa]-receptors in cocaine dependence and implicate [Kappa]-receptors as a potential therapeutic target. Part 2 : Chronic mild stress (footshocks: 0.5 mA, 20 min/session : 10 min after each hour of self-administration) during cocaine self- administration sessions (2 h/day) produced a significant escalation in cocaine intake in rats. This data suggests that stress is a factor that contributes to drug addiction. Western blot analysis revealed that in the nucleus accumbens (NAc) core, phosphorylation of GluR1at serine 845 was significantly decreased in stressed subjects in comparison to non-stressed subjects and in the NAc shell, phosphorylation of ERK1/2 was increased in subjects undergoing cocaine withdrawal. Extended access to cocaine as well as exposure to stress are environmental factors that have each been shown to cause increased cocaine intake, which can be indicative of a transition to drug addictio