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

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 hyper‐excitability 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 non‐canonical intracellular signaling pathways and present a theoretical molecular model in which the activation of several kinase effectors, including PKCs, ERK and 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 agent...
Source: Genes, Brain and Behavior - Category: Genetics & Stem Cells Authors: Tags: REVIEW Source Type: research