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Interactions of cocaine with dopamine D(2)-like antagonists in squirrel monkeys.
MedLine Citation:
PMID:  23192312     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
RATIONALE: Studies investigating dopamine D(2) receptor antagonism of cocaine's discriminative stimulus effects have resulted in varied effects possibly due to the use of different antagonists, species, and procedures. OBJECTIVES: The present study sought to further investigate D(2) antagonism of cocaine's discriminative stimulus effects using a variety of D(2) antagonists and multiple doses of the antagonists in combination with cocaine. METHODS: The benzamide D(2) antagonists, eticlopride, raclopride, and sulpiride, and the butyrophenone D(2) antagonists haloperidol and spiperone were administered alone and in combination with cocaine in squirrel monkeys trained to discriminate cocaine from saline under a fixed-ratio food reinforcement procedure. RESULTS: All the D(2) antagonists, except haloperidol, antagonized the discriminative stimulus effects of the cocaine training dose. However, only the benzamide D(2) antagonists produced significant rightward shifts in the cocaine discriminative stimulus dose-effect curve and they only did so within a narrow dose range and time after administration. In contrast, the D(2) antagonists failed to antagonize the rate-suppressant effects of cocaine, and in some cases, cocaine appeared to antagonize the rate-suppressant effects of the antagonists. CONCLUSIONS: The present results suggest (1) that D(2) antagonism of cocaine's discriminative stimulus effects depends critically on the selected antagonist, antagonist dose, and time of administration, as well as how antagonism is assessed (i.e., in terms of effects on training dose or on the cocaine dose-effect curve), (2) that the maximal shift in cocaine's discriminative stimulus dose-effect curve possible with D(2) antagonists under these procedures is ~two- to threefold, and (3) that different effects of cocaine are differentially sensitive to dopamine receptor antagonism.
Authors:
Paul L Soto; Jonathan L Katz
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-29
Journal Detail:
Title:  Psychopharmacology     Volume:  -     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Behavioral Biology, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Suite 3000, Johns Hopkins Bayview Campus, Baltimore, MD, 21224-6823, USA, psoto@jhmi.edu.
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