Document Detail

The effects of eticlopride and the selective D3-antagonist PNU 99194-A on food- and cocaine-maintained responding in rhesus monkeys.
MedLine Citation:
PMID:  16631246     Owner:  NLM     Status:  MEDLINE    
The dopamine D3 receptor is mainly expressed in regions of the brain associated with the limbic system. D3 receptor blockade may antagonize cocaine reinforcement while producing less severe extrapyramidal side effects than blockade of D2 receptors. The purpose of the present studies was to evaluate the effects of a selective D3 receptor antagonist and a non-selective D2/D3 receptor antagonist on food- and cocaine-maintained responding under two schedules of cocaine self-administration. Adult male rhesus monkeys were trained to respond under multiple schedules of food (1.0 g pellets) and cocaine (0.01-0.3 mg/kg/injection) presentation. In one experiment (n=4), the schedule was a fixed-interval (FI) 3-min and a second study (n=6) was conducted using a second-order fixed-ratio 5 (FI 6-min:S) schedule. The D3 antagonist PNU 99194-A (0.3-3.0 mg/kg), which is 14-fold selective for D3 relative to D2 receptors, or the D2/D3 antagonist eticlopride (0.001-0.03 mg/kg) was administered immediately prior to the experimental session for at least 5 consecutive sessions. Under the multiple FI 3-min schedule of food and cocaine presentation, PNU 99194-A and eticlopride decreased food- and cocaine-maintained responding in a dose-dependent manner and irrespective of cocaine dose. Under the multiple second-order schedule of food and cocaine presentation, at least one dose of PNU 99194-A and eticlopride decreased cocaine- and food-maintained responding. These findings indicate that PNU 99194-A can decrease operant responding in monkeys, but not in a manner that would suggest selectivity of cocaine- over food-maintained responding. Future studies with more selective D3 antagonists are needed to better address the role of this receptor subtype in cocaine addiction.
Renee Claytor; Joshua A Lile; Michael A Nader
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-05-02
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  83     ISSN:  0091-3057     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-05-25     Completed Date:  2006-08-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  456-64     Citation Subset:  IM    
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA.
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MeSH Terms
Behavior, Animal / drug effects
Cocaine / administration & dosage
Dopamine Antagonists / pharmacology*
Indans / pharmacology*
Macaca mulatta
Receptors, Dopamine D2 / antagonists & inhibitors
Receptors, Dopamine D3 / antagonists & inhibitors
Reinforcement (Psychology)*
Reinforcement Schedule
Salicylamides / pharmacology*
Self Administration
Grant Support
Reg. No./Substance:
0/Dopamine Antagonists; 0/Indans; 0/Receptors, Dopamine D2; 0/Receptors, Dopamine D3; 0/Salicylamides; 153570-58-2/(5,6-dimethoxyindan-2-yl)dipropylamine; 50-36-2/Cocaine; 84226-12-0/eticlopride

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