Research article summary (published 22 Nov 2008):

Insular hypocretin transmission regulates nicotine reward.

Full Abstract

Damage to the insular cortex can profoundly disrupt tobacco addiction in human smokers, reflected in spontaneous cessation of the tobacco habit and persistently decreased urge to smoke. Little is known concerning the neurobiological mechanisms through which the insula may control the maintenance of the tobacco habit. Emerging evidence suggests that hypocretin (orexin) transmission may play an important role in drug reinforcement processes, but its role in the rewarding actions of nicotine, considered the key addictive component of tobacco smoke, remains largely unexplored. Here we show that blockade of hypocretin transmission at hypocretin-1 (Hcrt-1; orexin-1) receptors decreases i.v. nicotine self-administration in rats and the motivation to obtain the drug. Blockade of Hcrt-1 receptors also abolished the stimulatory effects of nicotine on brain reward circuitries, as measured by reversal of nicotine-induced lowering of intracranial self-stimulation thresholds. In addition, we show that hypocretin-containing fibers innervate the insula, Hcrt-1 receptors are located on insular cells, and blockade of Hcrt-1 receptors in the insula but not in the adjacent somatosensory cortex decreases nicotine self-administration. These data demonstrate that insular hypocretin transmission plays a permissive role in the motivational properties of nicotine, and therefore may be a key neurobiological substrate necessary for maintaining tobacco addiction in human smokers.

Author information

Author/s: Hollander, Jonathan A (JA); Lu, Qun (Q); Cameron, Michael D (MD); Kamenecka, Theodore M (TM); Kenny, Paul J (PJ);

Affiliation: Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458, USA.

Grants: DA020686 (Agency:NIDA NIH HHS) ; DA023915 (Agency:NIDA NIH HHS) ; DA024932 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2008-Dec; vol 105 (issue 49) : pp 19480-5

Dates: Created 2008/12/10; Completed 2009/01/30; Revised 2009/06/10;

PMID: 19033203, status: MEDLINE (last retrieved date: 6/11/2009)

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

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Benzoxazoles - pharmacokinetics Cerebral Cortex - drug effects; metabolism Intracellular Signaling Peptides and Proteins - metabolism Male Motivation Neuropeptides - metabolism Nicotine - pharmacology Nicotinic Agonists - pharmacology Rats

Rats Rats, Wistar Receptors, G-Protein-Coupled - metabolism Receptors, Neuropeptide - metabolism Reward Self Administration Smoking - metabolism Synaptic Transmission - physiology Tobacco Use Disorder - metabolism Urea - analogs & derivatives; pharmacokinetics

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea (0) ; Benzoxazoles (0) ; Intracellular Signaling Peptides and Proteins (0) ; Neuropeptides (0) ; Nicotinic Agonists (0) ; Receptors, G-Protein-Coupled (0) ; Receptors, Neuropeptide (0) ; orexin receptors (0) ; orexins (0) ; Nicotine (54-11-5) ; Urea (57-13-6)

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