Nicotine-induced upregulation of nicotinic receptors: Underlying mechanisms and relevance to nicotine addiction

• Published in: Biochemical pharmacology Vol. 78; no. 7; pp. 756 - 765
• Main Authors: Govind, Anitha P., Vezina, Paul, Green, William N.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01-10-2009; Elsevier
• Subjects: Action Potentials; Addiction; Animals; Biological and medical sciences; Dopamine - physiology; Humans; Medical sciences; Neurons - physiology; Nicotine - pharmacology; Nicotinic; Nucleus Accumbens - drug effects; Nucleus Accumbens - physiopathology; Pharmacology. Drug treatments; Protein Conformation; Protein Processing, Post-Translational; Protein Subunits - biosynthesis; Protein Subunits - chemistry; Protein Transport; Receptors; Receptors, Nicotinic - biosynthesis; Receptors, Nicotinic - chemistry; Sensitization; Subtypes; Tobacco Use Disorder - metabolism; Tobacco Use Disorder - physiopathology; Tobacco, tobacco smoking; Toxicology; Up-Regulation; Upregulation; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - physiopathology; Nicotinic; Subtypes; Receptors; Sensitization; Addiction; Upregulation; Tobacco smoking; Alkaloid; Cholinergic receptor; Drug of abuse; Mechanism of action; Nicotinic receptor; Subtype; Nicotine; Biological receptor
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2009.06.011

Potential mechanisms underlying nicotine-induced upregulation of nAChRs.
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.