PI3K activation within ventromedial prefrontal cortex regulates the expression of drug ‐seeking in two rodent species

A history of behaviorally contingent or noncontingent cocaine experience increased indices of PI3K activity within the ventromedial prefrontal cortex (vmPFC). Neuropharmacological inhibition of vmPFC PI3K activity reversed a cocaine ‐conditioned place‐preference in mice and blocked incubated cocaine‐seeking in rats. AbstractPhosphatidylinositide 3 ‐kinases (PI3Ks) are intracellular signal transducer enzymes that recruit protein kinase B (aka Akt) to the cell membrane, the subsequent activation of which regulates many cellular functions. PI3K/Akt activity is up‐regulated within mesocorticolimbic structures in animal models of alcoholism, b ut less is known regarding PI3K/Akt activity in animal models of cocaine addiction. Given that prefrontal cortex (PFC) is grossly dysregulated in addiction, we studied how cocaine affects protein indices of PFC PI3K/Akt activity in rat and mouse models and examined the relevance of PI3K activity for cocaine‐related learning. Immunoblotting of mouse medial PFC at 3 weeks withdrawal from a cocaine‐sensitization regimen (seven injections of 30 mg/kg, intraperitoneal [IP]) revealed increased kinase activity, as did immunoblotting of tissue from the ventral PFC of rats with a history of long‐ access intravenous cocaine self‐administration (0.25 mg/0.1 mL infusion; 10 days of 6 h/d cocaine access). Interestingly, increased Akt phosphorylation was observed in rat ventromedial PFC at both 3‐ and 30‐day withdrawal only in ...
Source: Addiction Biology - Category: Addiction Authors: Tags: ORIGINAL ARTICLE Source Type: research