Cocaine craving during protracted withdrawal requires PKCε priming within vmPFC

Addiction Biology
Bailey W MillerKaren K Szumlinski

Abstract

In individuals with a history of drug taking, the capacity of drug-associated cues to elicit indices of drug craving intensifies or incubates with the passage of time during drug abstinence. This incubation of cocaine craving, as well as difficulties with learning to suppress drug-seeking behavior during protracted withdrawal, are associated with a time-dependent deregulation of ventromedial prefrontal cortex (vmPFC) function. As the molecular bases for cocaine-related vmPFC deregulation remain elusive, the present study assayed the consequences of extended access to intravenous cocaine (6 hours/day; 0.25 mg/infusion for 10 day) on the activational state of protein kinase C epsilon (PKCε), an enzyme highly implicated in drug-induced neuroplasticity. The opportunity to engage in cocaine seeking during cocaine abstinence time-dependently altered PKCε phosphorylation within vmPFC, with reduced and increased p-PKCε expression observed in early (3 days) and protracted (30 days) withdrawal, respectively. This effect was more robust within the ventromedial versus dorsomedial PFC, was not observed in comparable cocaine-experienced rats not tested for drug-seeking behavior and was distinct from the rise in phosphorylated extracellular s...Continue Reading

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Citations

May 7, 2016·Nature Reviews. Neuroscience·Marina E Wolf
Aug 23, 2016·Journal of Neuroscience Research·Marek Schwendt, M Foster Olive
Jul 1, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Alvin S ChiuKaren K Szumlinski
Dec 1, 2020·Pharmacology, Biochemistry, and Behavior·Rachel D AltshulerXuan Li

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