Nicotine-induced upregulation of nicotinic receptors: underlying mechanisms and relevance to nicotine addiction.
A major hurdle in defining the molecular biology of nicotine addiction has been characterizing the different nicotinic acetylcholine receptor (nAChR) subtypes in the brain and how nicotine alters their function. Mounting evidence suggests that the addictive effects of nicotine, like other drugs of abuse, occur through interactions with its receptors in the mesolimbic dopamine system, particularly ventral tegmental area (VTA) neurons, where nicotinic receptors act to modulate the release of dopamine. The molecular identity of the nicotinic receptors responsible for drug seeking behavior, their cellular and subcellular location and the mechanisms by which these receptors initiate and maintain addiction are poorly defined. In this commentary, we review how nicotinic acetylcholine receptors (nAChRs) are upregulated by nicotine exposure, the potential posttranslational events that appear to cause it and how upregulation is linked to nicotine addiction.
Govind
Anitha P
AP
Department of Neurobiology, University of Chicago, Abbot Hall 402-MC0926, Chicago, IL 60637, USA. apgovind@uchicago.edu
Vezina
Paul
P
Green
William N
WN
D000200:Action Potentials; D000818:Animals; D004298:Dopamine / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000096:biosynthesis / Q000737:chemistry; D021381:Protein Transport; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000737:chemistry; D014029:Tobacco Use Disorder / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology
D021122:Protein Subunits; D011978:Receptors, Nicotinic; D009538:Nicotine; D004298:Dopamine