The nucleus accumbens: Mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis

M. D. Scofield, J. A. Heinsbroek, Cassandra Gipson-Reichardt, Y. M. Kupchik, S. Spencer, A. C W Smith, D. Roberts-Wolfe, P. W. Kalivas

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goaldirected behaviors. Chronic exposure to several classes of drugs of abuse disrupts plasticity in this region, allowing drug-associated cues to engender a pathologic motivation for drug seeking.Anumber of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These druginduced neuroadaptations serve as the molecular basis for relapse vulnerability. In this review, we focus on the role that glutamate signal transduction in the nucleus accumbens plays in addiction-related behaviors. First, we explore the nucleus accumbens, including the cell types and neuronal populations present as well as afferent and efferent connections. Next we discuss rodent models of addiction and assess the viability of these models for testing candidate pharmacotherapies for the prevention of relapse. Then we provide a review of the literature describing how synaptic plasticity in the accumbens is altered after exposure to drugs of abuse and withdrawal and also how pharmacological manipulation of glutamate systems in the accumbens can inhibit drug seeking in the laboratory setting. Finally, we examine results from clinical trials in which pharmacotherapies designed to manipulate glutamate systems have been effective in treating relapse in human patients. Further elucidation of how drugs of abuse alter glutamatergic plasticity within the accumbens will be necessary for the development of new therapeutics for the treatment of addiction across all classes of addictive substances.

Original languageEnglish (US)
Pages (from-to)816-871
Number of pages56
JournalPharmacological Reviews
Volume68
Issue number3
DOIs
StatePublished - Jul 1 2016

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Nucleus Accumbens
Substance-Related Disorders
Glutamic Acid
Street Drugs
Homeostasis
Pharmaceutical Preparations
Recurrence
Drug Therapy
Neuronal Plasticity
Secondary Prevention
Basal Ganglia
Cues
Motivation
Rodentia
Signal Transduction
Clinical Trials
Pharmacology
Therapeutics
Population

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

The nucleus accumbens : Mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis. / Scofield, M. D.; Heinsbroek, J. A.; Gipson-Reichardt, Cassandra; Kupchik, Y. M.; Spencer, S.; Smith, A. C W; Roberts-Wolfe, D.; Kalivas, P. W.

In: Pharmacological Reviews, Vol. 68, No. 3, 01.07.2016, p. 816-871.

Research output: Contribution to journalArticle

Scofield, MD, Heinsbroek, JA, Gipson-Reichardt, C, Kupchik, YM, Spencer, S, Smith, ACW, Roberts-Wolfe, D & Kalivas, PW 2016, 'The nucleus accumbens: Mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis', Pharmacological Reviews, vol. 68, no. 3, pp. 816-871. https://doi.org/10.1124/pr.116.012484
Scofield, M. D. ; Heinsbroek, J. A. ; Gipson-Reichardt, Cassandra ; Kupchik, Y. M. ; Spencer, S. ; Smith, A. C W ; Roberts-Wolfe, D. ; Kalivas, P. W. / The nucleus accumbens : Mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis. In: Pharmacological Reviews. 2016 ; Vol. 68, No. 3. pp. 816-871.
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