Kinase interest you in treating incubated cocaine-craving? A hypothetical model for treatment intervention during protracted withdrawal from cocaine.

Autor: Szumlinski KK; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, California.; Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California., Shin CB; Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, California.
Jazyk: angličtina
Zdroj: Genes, brain, and behavior [Genes Brain Behav] 2018 Mar; Vol. 17 (3), pp. e12440. Date of Electronic Publication: 2017 Dec 20.
DOI: 10.1111/gbb.12440
Abstrakt: A diagnostic criterion for drug addiction, persistent drug-craving continues to be the most treatment-resistant aspect of addiction that maintains the chronic, relapsing, nature of this disease. Despite the high prevalence of psychomotor stimulant addiction, there currently exists no FDA-approved medication for craving reduction. In good part, this reflects our lack of understanding of the neurobiological underpinnings of drug-craving. In humans, cue-elicited drug-craving is associated with the hyperexcitability of prefrontal cortical regions. Rodent models of cocaine addiction indicate that a history of excessive cocaine-taking impacts excitatory glutamate signaling within the prefrontal cortex to drive drug-seeking behavior during protracted withdrawal. This review summarizes evidence that the capacity of cocaine-associated cues to augment craving in highly drug-experienced rats relates to a withdrawal-dependent incubation of glutamate release within prelimbic cortex. We discuss how stimulation of mGlu1/5 receptors increases the activational state of both canonical and noncanonical intracellular signaling pathways and present a theoretical molecular model in which the activation of several kinase effectors, including protein kinase C, extracellular signal-regulated kinase and phosphoinositide 3-kinase (PI3K) might lead to receptor desensitization to account for persistent cocaine-craving during protracted withdrawal. Finally, this review discusses the potential for existing, FDA-approved, pharmacotherapeutic agents that target kinase function as a novel approach to craving intervention in cocaine addiction.
(© 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)
Databáze: MEDLINE
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