Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats.

Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats. Research Abstract Details 

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Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats. Abstract Text:

Ryan F Yoshimura,Derk J Hogenkamp,Wen Y Li,Minhtam B Tran,James D Belluzzi,Edward R Whittemore,Frances M Leslie,Kelvin W Gee,Ryan F Yoshimura,Derk J Hogenkamp,Wen Y Li,Minhtam B Tran,James D Belluzzi,Edward R Whittemore,Frances M Leslie,Kelvin W Gee,

Drugs that antagonize nicotinic acetylcholine receptors (nAChRs) can be used to inhibit nicotine-induced behavior in both humans and animals. The aim of our experiments is to establish a proof-of-principle that antagonism of nAChRs by negative allosteric modulation can alter behavior in a relevant animal model of addiction, nicotine self-administration. We have identified a novel, negative allosteric modulator of nAChRs, UCI-30002 [N-(1,2,3,4-tetrahydro-1-naphthyl)-4-nitroaniline], with selectivity for the major neuronal nAChR subtypes over muscle-type nAChRs. After systemic administration, UCI-30002 significantly reduces nicotine self-administration in rats on both fixed ratio and progressive ratio schedules of reinforcement. The minimum effective dose that significantly alters nicotine self-administration corresponds to brain concentrations of UCI-30002 that produce at least 30% inhibition of the major neuronal nAChR subtypes measured in vitro. UCI-30002 has no effect on responding for food reinforcement in rats on either type of schedule, indicating that there is no effect on general responding or natural reward. UCI-30002 represents validation of the concept that negative allosteric modulators may have significant benefits as a strategy for treating nicotine addiction and encourages the development of subtype-selective modulators.

Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats. Publishing Authors By Initials

RF Yoshimura,DJ Hogenkamp,WY Li,MB Tran,JD Belluzzi,ER Whittemore,FM Leslie,KW Gee,RF Yoshimura,DJ Hogenkamp,WY Li,MB Tran,JD Belluzzi,ER Whittemore,FM Leslie,KW Gee,

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Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of pharmacology and experimental thera

VOLUME: 323

Page Numbers: 907-15

Journal Abbreviation: J. Pharmacol. Exp. Ther.

ISSN: 1521-0103

DAY: 14

MONTH: 09

YEAR: 2007

Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats. Information

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LANGUAGE: eng

NlmUniqueID: 376362

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Grant and Affiliation Information for Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats.

AFFILIATION: Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA.

Country: United States

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MEDLINETA: J Pharmacol Exp Ther

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