Document Detail


The effects of chronic versus acute desipramine on nicotine withdrawal and nicotine self-administration in the rat.
MedLine Citation:
PMID:  18438738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Nicotine withdrawal is characterized by depression-like symptomatology that may be mediated by dysregulations in norepinephrine transmission. These aversive aspects of nicotine withdrawal and the rewarding effects of nicotine play major roles in maintaining nicotine dependence.
OBJECTIVES: The aim of this work was to evaluate the effects of desipramine (DMI), a preferential norepinephrine reuptake inhibitor and antidepressant, on preclinical models of nicotine dependence in rats.
MATERIALS AND METHODS: A rate-independent current-intensity discrete-trial threshold intracranial self-stimulation procedure was used to assess brain reward function during nicotine withdrawal induced by cessation of nicotine infusion via subcutaneous osmotic mini pumps (3.16 mg/kg/day, base). Nicotine withdrawal was also measured by somatic signs of withdrawal. DMI was administered acutely (2 or 5 mg/kg, salt) during nicotine/saline withdrawal. In other naïve rats, chronic DMI treatment via mini pump (15 mg/kg/day, salt) began after 7 days of nicotine/saline exposure and continued during administration of nicotine/saline for 14 days and during nicotine/saline withdrawal. Additional rats acquired intravenous nicotine- or food-maintained responding, were prepared with DMI/vehicle-containing mini pumps, and self-administered nicotine or food during 12 days of DMI/vehicle exposure.
RESULTS: Acute DMI administration had no effect on threshold elevations observed in nicotine-withdrawing rats. Chronic DMI administration prevented the reward threshold elevations and the increased somatic signs of nicotine withdrawal. Although chronic DMI significantly decreased nicotine self-administration, it also decreased food-maintained responding.
CONCLUSIONS: The results suggest that norepinephrine reuptake inhibitors may be effective anti-smoking treatments that reduce the anhedonic depression-like and somatic components of nicotine withdrawal and may alter the rewarding effects of nicotine and food.
Authors:
Neil E Paterson; Svetlana Semenova; Athina Markou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-04-29
Journal Detail:
Title:  Psychopharmacology     Volume:  198     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-22     Completed Date:  2008-11-17     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  351-62     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidepressive Agents, Tricyclic / therapeutic use*
Conditioning, Operant / drug effects
Depression / psychology
Desipramine / therapeutic use*
Food
Infusion Pumps, Implantable
Injections, Intravenous
Nicotine / administration & dosage,  pharmacology*
Nicotinic Agonists / administration & dosage,  pharmacology*
Rats
Reward
Self Administration
Self Stimulation
Substance Withdrawal Syndrome / drug therapy*,  psychology*
Tobacco Use Disorder / drug therapy*,  psychology
Grant Support
ID/Acronym/Agency:
R01 MH062527/MH/NIMH NIH HHS; R01 MH062527-06/MH/NIMH NIH HHS; R01 MH62527/MH/NIMH NIH HHS; U01 MH069062/MH/NIMH NIH HHS; U01 MH069062-05/MH/NIMH NIH HHS; U01 MH069062-050002/MH/NIMH NIH HHS; U01 MH69062/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Antidepressive Agents, Tricyclic; 0/Nicotinic Agonists; 54-11-5/Nicotine; TG537D343B/Desipramine
Comments/Corrections

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