Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice.

Full Abstract

In humans, tobacco withdrawal produces symptoms that contribute to the difficulty associated with smoking cessation. Nicotine withdrawal symptoms can also be observed in rodents. A major standing question is which nicotinic receptor subtypes and which areas of the brain are necessary for nicotine withdrawal to occur. Using knock-out mice, we previously showed that the beta4, but not the beta2 subunit of nicotinic acetylcholine receptors, is necessary for the somatic manifestations of nicotine withdrawal. Since the beta4 subunit is highly expressed in the medial habenula, we focused our studies on the medial habenula and its primary target, the interpeduncular nucleus. In particular, we studied nicotine withdrawal in mice lacking the alpha2 or the alpha5 nicotinic receptor subunits, which are highly expressed in the interpeduncular nucleus. We precipitated withdrawal by systemically injecting the nicotinic antagonist mecamylamine in mice chronically treated with nicotine. Both the alpha2 and the alpha5 null mutations abolished the somatic manifestations of nicotine withdrawal. In addition, in wild-type mice chronically treated with nicotine, mecamylamine precipitated withdrawal when microinjected into the habenula or the interpeduncular nucleus, but not into the cortex, ventral tegmental area or hippocampus. Our results demonstrate a major role for the habenulo-interpeduncular system and the nicotinic receptor subunits expressed therein, in nicotine withdrawal symptoms. Our data suggest that the efforts to develop new smoking cessation therapies should concentrate on these areas and receptor types.

Author information

Author/s: Salas, Ramiro (R); Sturm, Renea (R); Boulter, Jim (J); De Biasi, Mariella (M);

Affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.

Grants: DA017173 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Mar; vol 29 (issue 10) : pp 3014-8

Dates: Created 2009/03/12; Completed 2009/04/10;

PMID: 19279237, status: MEDLINE (last retrieval date: 4/10/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Mice, Mutant Strains
Nicotine - metabolism; pharmacology
Nicotinic Antagonists - pharmacology
Protein Subunits - agonists; antagonists & inhibitors; biosynthesis; deficiency
Receptors, Nicotinic - biosynthesis; deficiency
Substance Withdrawal Syndrome - genetics; metabolism
Tegmentum Mesencephali - drug effects; metabolism

Associated Chemicals: Nicotinic Antagonists (0) ; Protein Subunits (0) ; Receptors, Nicotinic (0) ; Nicotine (54-11-5)

This article has not been indexed for related articles as yet, however you can still use the live related article search links below.

See 100+ related articles.

See a large map of 100+ related articles.