Glutamatergic substrates of drug addiction and alcoholism

Justin T. Gass, Michael Olive

Research output: Contribution to journalArticle

341 Citations (Scopus)

Abstract

The past two decades have witnessed a dramatic accumulation of evidence indicating that the excitatory amino acid glutamate plays an important role in drug addiction and alcoholism. The purpose of this review is to summarize findings on glutamatergic substrates of addiction, surveying data from both human and animal studies. The effects of various drugs of abuse on glutamatergic neurotransmission are discussed, as are the effects of pharmacological or genetic manipulation of various components of glutamate transmission on drug reinforcement, conditioned reward, extinction, and relapse-like behavior. In addition, glutamatergic agents that are currently in use or are undergoing testing in clinical trials for the treatment of addiction are discussed, including acamprosate, N-acetylcysteine, modafinil, topiramate, lamotrigine, gabapentin and memantine. All drugs of abuse appear to modulate glutamatergic transmission, albeit by different mechanisms, and this modulation of glutamate transmission is believed to result in long-lasting neuroplastic changes in the brain that may contribute to the perseveration of drug-seeking behavior and drug-associated memories. In general, attenuation of glutamatergic transmission reduces drug reward, reinforcement, and relapse-like behavior. On the other hand, potentiation of glutamatergic transmission appears to facilitate the extinction of drug-seeking behavior. However, attempts at identifying genetic polymorphisms in components of glutamate transmission in humans have yielded only a limited number of candidate genes that may serve as risk factors for the development of addiction. Nonetheless, manipulation of glutamatergic neurotransmission appears to be a promising avenue of research in developing improved therapeutic agents for the treatment of drug addiction and alcoholism.

Original languageEnglish (US)
Pages (from-to)218-265
Number of pages48
JournalBiochemical Pharmacology
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Alcoholism
Substance-Related Disorders
Glutamic Acid
Drug-Seeking Behavior
Street Drugs
Substrates
Reward
Synaptic Transmission
Pharmaceutical Preparations
Excitatory Amino Acid Agents
Memantine
Recurrence
Excitatory Amino Acids
Acetylcysteine
Genetic Polymorphisms
Reinforcement
Clinical Trials
Pharmacology
Surveying
Polymorphism

Keywords

  • Alcoholism
  • Drug addiction
  • Glutamate
  • Pharmacotherapeutics
  • Relapse
  • Synaptic plasticity

ASJC Scopus subject areas

  • Pharmacology

Cite this

Glutamatergic substrates of drug addiction and alcoholism. / Gass, Justin T.; Olive, Michael.

In: Biochemical Pharmacology, Vol. 75, No. 1, 01.01.2008, p. 218-265.

Research output: Contribution to journalArticle

@article{cee9ba66fd5c46c0b7be8fcae5006147,
title = "Glutamatergic substrates of drug addiction and alcoholism",
abstract = "The past two decades have witnessed a dramatic accumulation of evidence indicating that the excitatory amino acid glutamate plays an important role in drug addiction and alcoholism. The purpose of this review is to summarize findings on glutamatergic substrates of addiction, surveying data from both human and animal studies. The effects of various drugs of abuse on glutamatergic neurotransmission are discussed, as are the effects of pharmacological or genetic manipulation of various components of glutamate transmission on drug reinforcement, conditioned reward, extinction, and relapse-like behavior. In addition, glutamatergic agents that are currently in use or are undergoing testing in clinical trials for the treatment of addiction are discussed, including acamprosate, N-acetylcysteine, modafinil, topiramate, lamotrigine, gabapentin and memantine. All drugs of abuse appear to modulate glutamatergic transmission, albeit by different mechanisms, and this modulation of glutamate transmission is believed to result in long-lasting neuroplastic changes in the brain that may contribute to the perseveration of drug-seeking behavior and drug-associated memories. In general, attenuation of glutamatergic transmission reduces drug reward, reinforcement, and relapse-like behavior. On the other hand, potentiation of glutamatergic transmission appears to facilitate the extinction of drug-seeking behavior. However, attempts at identifying genetic polymorphisms in components of glutamate transmission in humans have yielded only a limited number of candidate genes that may serve as risk factors for the development of addiction. Nonetheless, manipulation of glutamatergic neurotransmission appears to be a promising avenue of research in developing improved therapeutic agents for the treatment of drug addiction and alcoholism.",
keywords = "Alcoholism, Drug addiction, Glutamate, Pharmacotherapeutics, Relapse, Synaptic plasticity",
author = "Gass, {Justin T.} and Michael Olive",
year = "2008",
month = "1",
day = "1",
doi = "10.1016/j.bcp.2007.06.039",
language = "English (US)",
volume = "75",
pages = "218--265",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Glutamatergic substrates of drug addiction and alcoholism

AU - Gass, Justin T.

AU - Olive, Michael

PY - 2008/1/1

Y1 - 2008/1/1

N2 - The past two decades have witnessed a dramatic accumulation of evidence indicating that the excitatory amino acid glutamate plays an important role in drug addiction and alcoholism. The purpose of this review is to summarize findings on glutamatergic substrates of addiction, surveying data from both human and animal studies. The effects of various drugs of abuse on glutamatergic neurotransmission are discussed, as are the effects of pharmacological or genetic manipulation of various components of glutamate transmission on drug reinforcement, conditioned reward, extinction, and relapse-like behavior. In addition, glutamatergic agents that are currently in use or are undergoing testing in clinical trials for the treatment of addiction are discussed, including acamprosate, N-acetylcysteine, modafinil, topiramate, lamotrigine, gabapentin and memantine. All drugs of abuse appear to modulate glutamatergic transmission, albeit by different mechanisms, and this modulation of glutamate transmission is believed to result in long-lasting neuroplastic changes in the brain that may contribute to the perseveration of drug-seeking behavior and drug-associated memories. In general, attenuation of glutamatergic transmission reduces drug reward, reinforcement, and relapse-like behavior. On the other hand, potentiation of glutamatergic transmission appears to facilitate the extinction of drug-seeking behavior. However, attempts at identifying genetic polymorphisms in components of glutamate transmission in humans have yielded only a limited number of candidate genes that may serve as risk factors for the development of addiction. Nonetheless, manipulation of glutamatergic neurotransmission appears to be a promising avenue of research in developing improved therapeutic agents for the treatment of drug addiction and alcoholism.

AB - The past two decades have witnessed a dramatic accumulation of evidence indicating that the excitatory amino acid glutamate plays an important role in drug addiction and alcoholism. The purpose of this review is to summarize findings on glutamatergic substrates of addiction, surveying data from both human and animal studies. The effects of various drugs of abuse on glutamatergic neurotransmission are discussed, as are the effects of pharmacological or genetic manipulation of various components of glutamate transmission on drug reinforcement, conditioned reward, extinction, and relapse-like behavior. In addition, glutamatergic agents that are currently in use or are undergoing testing in clinical trials for the treatment of addiction are discussed, including acamprosate, N-acetylcysteine, modafinil, topiramate, lamotrigine, gabapentin and memantine. All drugs of abuse appear to modulate glutamatergic transmission, albeit by different mechanisms, and this modulation of glutamate transmission is believed to result in long-lasting neuroplastic changes in the brain that may contribute to the perseveration of drug-seeking behavior and drug-associated memories. In general, attenuation of glutamatergic transmission reduces drug reward, reinforcement, and relapse-like behavior. On the other hand, potentiation of glutamatergic transmission appears to facilitate the extinction of drug-seeking behavior. However, attempts at identifying genetic polymorphisms in components of glutamate transmission in humans have yielded only a limited number of candidate genes that may serve as risk factors for the development of addiction. Nonetheless, manipulation of glutamatergic neurotransmission appears to be a promising avenue of research in developing improved therapeutic agents for the treatment of drug addiction and alcoholism.

KW - Alcoholism

KW - Drug addiction

KW - Glutamate

KW - Pharmacotherapeutics

KW - Relapse

KW - Synaptic plasticity

UR - http://www.scopus.com/inward/record.url?scp=36849072543&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36849072543&partnerID=8YFLogxK

U2 - 10.1016/j.bcp.2007.06.039

DO - 10.1016/j.bcp.2007.06.039

M3 - Article

C2 - 17706608

AN - SCOPUS:36849072543

VL - 75

SP - 218

EP - 265

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 1

ER -