The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis
| Autor: | Alexander C.W. Smith, P. W. Kalivas, Cassandra D. Gipson, Douglas Roberts-Wolfe, Jasper A. Heinsbroek, Sade Spencer, Michael D. Scofield, Yonatan M. Kupchik |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Substance-Related Disorders media_common.quotation_subject Glutamic Acid Nucleus accumbens Receptors Ionotropic Glutamate Nucleus Accumbens 03 medical and health sciences Glutamatergic 0302 clinical medicine Glutamate homeostasis Recurrence Vesicular Glutamate Transport Proteins Basal ganglia Animals Homeostasis Humans Medicine Molecular Targeted Therapy Review Articles media_common Neurons Pharmacology Neuronal Plasticity Illicit Drugs business.industry Addiction Glutamate receptor Behavior Addictive 030104 developmental biology Synaptic plasticity Molecular Medicine business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Pharmacological Reviews. 68:816-871 |
| ISSN: | 1521-0081 0031-6997 |
| DOI: | 10.1124/pr.116.012484 |
| Popis: | The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goal-directed 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. A number of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These drug-induced 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. |
| Databáze: | OpenAIRE |
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