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Cited by 349

The DOI matches its Crossref record; 155 of the 155 references it cites were found in a registry or an index.

New medications for drug addiction hiding in glutamatergic neuroplasticity

Open access
Kalivas, P W, Volkow, N D·2011·Molecular Psychiatry
DOI 10.1038/mp.2011.46
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Abstract

The repeated use of drugs that directly or indirectly stimulate dopamine transmission carry addiction liability and produce enduring pathological changes in the brain circuitry that normally regulates adaptive behavioral responding to a changing environment. This circuitry is rich in glutamatergic projections, and addiction-related behaviors in animal models have been linked to impairments in excitatory synaptic plasticity. Among the best-characterized glutamatergic projection in this circuit is the prefrontal efferent to the nucleus accumbens. A variety of molecular adaptations have been identified in the prefrontal glutamate synapses in the accumbens, many of which are induced by different classes of addictive drugs. Based largely on work with cocaine, we hypothesize that the drug-induced adaptations impair synaptic plasticity in the cortico-accumbens projection, and thereby dysregulate the ability of addicts to control their drug-taking habits. Accordingly, we go on to describe the literature implicating the drug-induced changes in protein content or function that impinge upon synaptic plasticity and have been targeted in preclinical models of relapse and, in some cases, in pilot clinical trials. Based upon modeling drug-induced impairments in neuroplasticity in the cortico-accumbens pathway, we argue for a concerted effort to clinically evaluate the hypothesis that targeting glial and neuronal proteins regulating excitatory synaptic plasticity may prove beneficial in treating addiction.

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Metadata

Authors
Kalivas, P. W., & Volkow, N. D.
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2011-04-26
Volume
16
Issue
10
Pages
974-986
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2011.46
OpenAlex
W2019860362
Cited by
349
References
155
FWCI
11.55
Type
journal article
Language
en
Open access
green

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