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: Karen K. Szumlinski,
Alexis W. Ary,
Christina B. Shin,
Melissa G. Wroten,
Justin Courson,
Bailey W. Miller,
Micaela Ruppert ‐Majer,
John W. Hiller,
John R. Shahin,
Osnat Ben‐Shahar,
Tod E. Kippin Tags: ORIGINAL ARTICLE Source Type: research
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