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Metabotropic Glutamate Receptors as Targets for the Treatment of Drug and Alcohol Dependence

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Glutamate-based Therapies for Psychiatric Disorders

Part of the book series: Milestones in Drug Therapy ((MDT))

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Abstract

Experimental studies in laboratory animals discussed in this chapter demonstrate the involvement of various metabotropic glutamate receptors (mGluRs) in different aspects of drug and alcohol dependence. Postsynaptic mGluR5 antagonists and inhibitory presynaptic mGluR2/3 agonists decreased drug self-administration and attenuated reinstatement of drug-seeking behavior by reducing the increases in glutamate transmission induced by drugs of abuse or the presentation of stimuli previously associated with the drug effects or availability. These findings suggest that medications decreasing glutamatergic transmission may reduce the reinforcing and motivational properties of drugs of abuse and prevent relapse to drug taking in humans. mGluR2/3 antagonists may be useful in the treatment of depressive-like affective symptoms of drug withdrawal by reversing the hypothesized decrease in glutamate transmission that occurs during psychostimulant, but not opiate, withdrawal. The potential of these compounds as medications for drug and alcohol dependence remains to be evaluated in humans.

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Acknowledgments

This work was supported by National Institute on Drug Abuse grants (R01) DA11946 and (R01) DA023209 to Athina Markou. Both authors have a patent application regarding the use of mGluR compounds for the treatment of drug addiction. The authors have no other conflicts of interest to declare that are directly relevant to the content of this chapter. The authors would like to thank Mr. Michel Arends for editorial assistance and Ms. Janet Hightower for computer graphics.

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  1. Department of Psychiatry, School of Medicine, University of California San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA, 92093-0603, USA

    Athina Markou

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  1. Svetlana Semenova
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Correspondence to Athina Markou .

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  1. Div Pharmacotherapies & Medical Conseque, National Institute on Drug Abuse, Executive Boulevard 6001, Rockville, 20852, Maryland, USA

    Phil Skolnick

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Semenova, S., Markou, A. (2010). Metabotropic Glutamate Receptors as Targets for the Treatment of Drug and Alcohol Dependence. In: Skolnick, P. (eds) Glutamate-based Therapies for Psychiatric Disorders. Milestones in Drug Therapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0346-0241-9_8

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