Document Detail


Blockade of dopamine d4 receptors attenuates reinstatement of extinguished nicotine-seeking behavior in rats.
MedLine Citation:
PMID:  22030716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It has been reported that polymorphism of the DRD4 gene in humans is associated with reactivity to cues related to tobacco smoking. However, the role of DRD4 in animal models of nicotine addiction has seldom been explored. In our study, male Long-Evans rats learned to intravenously self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Effects of the selective DRD4 antagonist L-745,870 were evaluated on nicotine self-administration behavior and on reinstatement of extinguished nicotine-seeking behavior induced by nicotine-associated cues or by priming injections of nicotine. L-745,870 was also tested on reinstatement of extinguished food-seeking behavior as a control. In addition, the selective DRD4 agonist PD 168,077 was tested for its ability to reinstate extinguished nicotine-seeking behavior. Finally, L-745,870 was tested in Sprague Dawley rats trained to discriminate administration of 0.4 mg/kg nicotine from vehicle under an FR schedule of food delivery. L-745,870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast, L-745,870 did not affect established nicotine self-administration behavior or reinstatement of food-seeking behavior induced by food cues or food priming. L-745,870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168,077 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745,870 selectively attenuated both cue- and nicotine-induced reinstatement of nicotine-seeking behavior, without affecting cue- or food-induced reinstatement of food-seeking behavior, DRD4 antagonists are potential therapeutic agents against tobacco smoking relapse.
Authors:
Yijin Yan; Abhiram Pushparaj; Yann Le Strat; Islam Gamaleddin; Chanel Barnes; Zuzana Justinova; Steven R Goldberg; Bernard Le Foll
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2011-10-26
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  37     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-13     Completed Date:  2012-07-19     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  685-96     Citation Subset:  IM    
Affiliation:
Translational Addiction Research Laboratory, Centre for Addiction and Mental Health Addiction (CAMH), University of Toronto, Toronto, ON, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal / drug effects*
Discrimination Learning / drug effects
Dopamine Antagonists / pharmacology
Drug-Seeking Behavior / drug effects*
Extinction, Psychological / drug effects*
Male
Nicotine / administration & dosage*
Pyridines / pharmacology
Pyrroles / pharmacology
Rats
Rats, Long-Evans
Rats, Sprague-Dawley
Receptors, Dopamine D4 / antagonists & inhibitors*
Reinforcement (Psychology)
Self Administration
Grant Support
ID/Acronym/Agency:
N01 DA059909/DA/NIDA NIH HHS; ZIA DA000003-25/DA/NIDA NIH HHS; //Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; 0/Dopamine Antagonists; 0/Pyridines; 0/Pyrroles; 137750-34-6/Receptors, Dopamine D4; 54-11-5/Nicotine
Comments/Corrections

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