Review

Nature Reviews Neuroscience 10, 561-572 (August 2009) | doi:10.1038/nrn2515

The glutamate homeostasis hypothesis of addiction

Peter W. Kalivas1  About the author

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Addiction is associated with neuroplasticity in the corticostriatal brain circuitry that is important for guiding adaptive behaviour. The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use. A failure of the prefrontal cortex to control drug-seeking behaviours can be linked to an enduring imbalance between synaptic and non-synaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.

Author affiliations

  1. 173 Ashley Avenue, BSB 410, Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
    Email: kalivasp@musc.edu

Published online 1 July 2009

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