Yonsei Med J.  2008 Apr;49(2):175-188. 10.3349/ymj.2008.49.2.175.

The Role of NMDA Receptor Antagonists in Nicotine Tolerance, Sensitization, and Physical Dependence: A Preclinical Review

• Jain R
• Mukherjee
• Balhara YP

• KMID: 1084488
• DOI: http://doi.org/10.3349/ymj.2008.49.2.175

Abstract

Nicotine, the primary psychoactive component of tobacco products, produces diverse neurophysiological, motivational, and behavioral effects through several brain regions and neurochemical pathways. Various neurotransmitter systems have been explored to understand the mechanisms behind nicotine tolerance, dependence, and withdrawal. Recent evidence suggests that glutamate neurotransmission has an important role in this phenomenon. The aim of the present review is to discuss preclinical findings concerning the role of N-methyl-D-aspartate (NMDA) receptor neurotransmission in mediating the behavioral effects of nicotine, tolerance, sensitization, dependence, and withdrawal. Based on preclinical findings, it is hypothesized that NMDA receptors mediate the common adaptive processes that are involved in the development, maintenance, and expression of nicotine addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists may prove to be useful in alleviating the symptoms of nicotine abstinence and facilitate tobacco-smoking cessation.

Keyword

Nicotine; NMDA receptors; tolerance; sensitization dependence

MeSH Terms

Animals
Dizocilpine Maleate/pharmacology
Drug Tolerance
Excitatory Amino Acid Antagonists/*pharmacology
Humans
Nicotine/*administration & dosage
Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/physiology
Substance Withdrawal Syndrome/physiopathology/prevention & control
Tobacco Use Disorder/physiopathology/*prevention & control

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