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Role of Cdk5 in Drug Abuse and Plasticity
Author(s) -
BENAVIDES DAVID R.,
BIBB JAMES A.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1316.041
Subject(s) - substance abuse , drug , medicine , psychology , medical emergency , psychiatry
A bstract : Neuronal plasticity serves as the basis for learning and memory in the adult brain. Contextual, motor, and reward‐based learning are important in reinforcing survival behavior in animals. Most psychostimulant drugs of abuse target the dopaminergic reward system of the brain. Drugs of abuse cause long‐standing cellular and molecular neuroadaptations in the brain. The neuronal protein kinase Cdk5 is emerging as an important player in the cellular and physiological responses to drugs of abuse. Substantial evidence indicates that Cdk5 controls dopamine neurotransmission through regulation of the protein phosphatase‐1 inhibitor, DARPP‐32. Furthermore, the morphological changes associated with chronic cocaine exposure are dependent on Cdk5. Thus, Cdk5 mediates cellular responses to psychostimulant drug‐induced changes in dopamine signal transduction and cytoskeletal reorganization. In this regard, Cdk5, through its targeting of various substrates, integrates a number of intracellular pathways that are targeted by psychostimulant drugs. These studies and the emerging role of Cdk5 in various forms of neuronal plasticity are reviewed.