Document Detail


Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal.
MedLine Citation:
PMID:  23624742     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Smoking is the largest preventable cause of death in the United States. Furthermore, a recent study found that <10% of quit attempts resulted in continuous abstinence for 1 year. With the introduction of pharmacotherapies like Chantix (varenicline), a selective α4β2 nicotinic partial agonist, successful quit attempts have significantly increased. Therefore, novel subtype-specific nicotinic drugs, such as sazetidine-A, present a rich area for investigation of therapeutic potential in smoking cessation. The present studies examine the anxiety-related behavioral and functional effects of the nicotinic partial agonists varenicline and sazetidine-A during withdrawal from chronic nicotine in mice. Our studies indicate that ventral hippocampal-specific infusions of sazetidine-A, but not varenicline, are efficacious in reducing nicotine withdrawal-related anxiety-like phenotypes in the novelty-induced hypophagia (NIH) paradigm. To further investigate functional differences between these partial agonists, we utilized voltage-sensitive dye imaging (VSDi) in ventral hippocampal slices to determine the effects of sazetidine-A and varenicline in animals chronically treated with saline, nicotine, or undergoing 24 h withdrawal. These studies demonstrate a functional dissociation of varenicline and sazetidine-A on hippocampal network activity, which is directly related to previous drug exposure. Furthermore, the effects of the nicotinic partial agonists in VSDi assays are significantly correlated with their behavioral effects in the NIH test. These findings highlight the importance of drug history in understanding the mechanisms through which nicotinic compounds may be aiding smoking cessation in individuals experiencing withdrawal-associated anxiety.
Authors:
Jill R Turner; Derek S Wilkinson; Rachel Lf Poole; Thomas J Gould; Gregory C Carlson; Julie A Blendy
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-04-29
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  38     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-08-16     Completed Date:  2014-03-24     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  2035-47     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anxiety / chemically induced,  drug therapy
Azetidines / administration & dosage,  pharmacology*,  therapeutic use
Benzazepines / administration & dosage,  pharmacology*
Cerebral Cortex / drug effects,  metabolism
Dose-Response Relationship, Drug
Drug Partial Agonism
Evoked Potentials / drug effects,  physiology
Hippocampus / drug effects,  metabolism,  physiology
Male
Mice
Microinjections
Motor Activity / drug effects
Nicotine / adverse effects*
Nicotinic Agonists / administration & dosage,  pharmacology*,  therapeutic use
Pyridines / administration & dosage,  pharmacology*,  therapeutic use
Quinoxalines / administration & dosage,  pharmacology*
Receptors, Nicotinic / metabolism
Smoking Cessation / methods
Substance Withdrawal Syndrome / drug therapy
Up-Regulation
Grant Support
ID/Acronym/Agency:
1-F32-DA026236/DA/NIDA NIH HHS; 1-K99-DA032681/DA/NIDA NIH HHS; DA024787-01A1S1/DA/NIDA NIH HHS; F32 DA026236/DA/NIDA NIH HHS; K99 DA032681/DA/NIDA NIH HHS; P50 CA143187/CA/NCI NIH HHS; P50-CA143187/CA/NCI NIH HHS; R01 DA024787/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Azetidines; 0/Benzazepines; 0/Nicotinic Agonists; 0/Pyridines; 0/Quinoxalines; 0/Receptors, Nicotinic; 0/sazetidine-A; 54-11-5/Nicotine; W6HS99O8ZO/varenicline
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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