The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review.
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.
Jain
Raka
R
National Drug Dependence Treatment Centre and Department of Psychiatry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, Pin 110029, India. rakajain2001@yahoo.com
Mukherjee
Kaushiki
K
Balhara
Yatan Pal Singh
YP
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004361:Drug Tolerance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D009538:Nicotine / Q000008:administration & dosage*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000517:prevention & control; D014029:Tobacco Use Disorder / Q000503:physiopathology / Q000517:prevention & control*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D009538:Nicotine