Document Detail


Effect of prazosin and guanfacine on stress-induced reinstatement of alcohol and food seeking in rats.
MedLine Citation:
PMID:  21318567     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE AND OBJECTIVES: Relapse to alcohol use during abstinence or maladaptive eating habits during dieting is often provoked by stress. The anxiogenic drug yohimbine, which causes stress-like responses in humans and non-humans, reliably reinstates alcohol and food seeking in a rat relapse model. Yohimibine is a prototypical alpha-2 adrenoceptor antagonist, but results from studies on noradrenaline's role in yohimbine-induced reinstatement of drug and food seeking are inconclusive. Here, we further addressed this issue by studying the effect of the alpha-1 adrenoceptor antagonist prazosin and the alpha-2 adrenoceptor agonist guanfacine on yohimbine-induced reinstatement.
METHODS: In exp. 1, we trained rats to self-administer alcohol (12% w/v, 1 h/day), and after extinction of alcohol-reinforced lever pressing, we tested prazosin's (0.5, 1.0, and 2.0 mg/kg, i.p.) or guanfacine's (0.125, 0.25, and 0.5 mg/kg, i.p.) effect on yohimbine (1.25 mg/kg, i.p.)-induced reinstatement; we also examined prazosin's effect on intermittent-footshock-stress-induced reinstatement. In exp. 2, we trained food-restricted rats to self-administer 45 mg food pellets and first examined prazosin's or guanfacine's effects on food-reinforced responding, and then, after extinction of lever presses, on yohimbine-induced reinstatement.
RESULTS: Prazosin (0.5-2.0 mg/kg) blocked yohimbine-induced reinstatement of food and alcohol seeking, as well as footshock-induced reinstatement of alcohol seeking. Guanfacine attenuated yohimbine-induced reinstatement of alcohol seeking at the highest dose (0.5 mg/kg), but its effect on yohimbine-induced reinstatement of food seeking was not significant. Neither prazosin nor guanfacine affected high-rate food-reinforced responding.
CONCLUSIONS: Results demonstrate an important role of postsynaptic alpha-1 adrenoceptors in stress-induced reinstatement of alcohol and food seeking.
Authors:
A D Lê; Douglas Funk; Walter Juzytsch; Kathleen Coen; Brittany M Navarre; Carlo Cifani; Yavin Shaham
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2011-02-12
Journal Detail:
Title:  Psychopharmacology     Volume:  218     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-12     Completed Date:  2012-02-08     Revised Date:  2013-02-19    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  89-99     Citation Subset:  IM    
Affiliation:
Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada. Anh_le@camh.net
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-1 Receptor Antagonists / administration & dosage,  pharmacology
Adrenergic alpha-2 Receptor Agonists / administration & dosage,  pharmacology
Adrenergic alpha-2 Receptor Antagonists / pharmacology
Animals
Conditioning, Operant / drug effects
Dose-Response Relationship, Drug
Ethanol / administration & dosage*
Feeding Behavior / drug effects*
Guanfacine / administration & dosage,  pharmacology*
Male
Prazosin / administration & dosage,  pharmacology*
Rats
Rats, Long-Evans
Rats, Wistar
Recurrence / prevention & control
Self Administration
Stress, Psychological
Yohimbine / pharmacology
Grant Support
ID/Acronym/Agency:
AA13108/AA/NIAAA NIH HHS; R01 AA013108-09/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic alpha-1 Receptor Antagonists; 0/Adrenergic alpha-2 Receptor Agonists; 0/Adrenergic alpha-2 Receptor Antagonists; 146-48-5/Yohimbine; 19216-56-9/Prazosin; 29110-47-2/Guanfacine; 64-17-5/Ethanol
Comments/Corrections

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


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