TY - JOUR
T1 - Glutamatergic substrates of drug addiction and alcoholism
AU - Gass, Justin T.
AU - Olive, M. Foster
N1 - Funding Information:
This work was supported by PHS grant AA013582 (MFO) and AA007474 (JTG) from the National Institute on Alcohol Abuse and Alcoholism, and a grant from the Alcoholic Beverage Medical Research Foundation (MFO).
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
SN - 0006-2952
VL - 75
SP - 218
EP - 265
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 1
ER -