Document Detail

Cocaine self-administration and locomotor activity are altered in Lewis and F344 inbred rats by RTI 336, a 3-phenyltropane analog that binds to the dopamine transporter.
MedLine Citation:
PMID:  16095575     Owner:  NLM     Status:  MEDLINE    
Lewis and Fischer 344 (F344) rats differ in responses to cocaine and characteristics of the mesolimbic dopamine system. Compared to F344 rats, Lewis rats have lower D2 receptor and dopamine transporter (DAT) levels in nucleus accumbens (NAc). We showed previously that altering D1 and D2 receptor levels pharmacologically had strain-dependent effects on cocaine self-administration. This study tests whether the phenyltropane analog, 3beta-(4-Chlorophenyl) tropane-2beta-[3-(4'-methylphenyl) isoxazol-5-yl] Hydrochloride (RTI 336), a potent and selective DAT inhibitor, differentially alters reinforcing, discriminative, and locomotor effects of cocaine in these strains. The effects of RTI 336 pretreatment on cocaine self-administration were assessed under a fixed-ratio (FR) schedule of reinforcement. Its effects on cocaine discrimination were conducted using a two-lever food-reinforced task. Finally, the effects of RTI 336 pretreatment on cocaine-induced locomotor activity were examined. RTI 336 increased cocaine self-administration in F344 rats, while Lewis rats showed reduced intake under the FR schedule. RTI 336 reduced cocaine-induced locomotor activity in Lewis rats but not in F344 rats. RTI 336 did not substitute for or antagonize cocaine's discriminative stimulus effects in either strain. Results show that a DAT inhibitor alters cocaine-induced behaviors in a strain-dependent manner. These effects may relate to inherent differences in NAc DAT levels between Lewis and F344 rats.
Colin N Haile; Xiang Yang Zhang; F Ivy Carroll; Therese A Kosten
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  1055     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-05     Completed Date:  2006-01-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  186-95     Citation Subset:  IM    
Department of Psychiatry, Division of Substance Abuse, Yale University School of Medicine, VA-CT Hospital System, 950 Campbell Avenue, Building 5; 3rd Floor, West Haven CT 06516, USA.
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MeSH Terms
Analysis of Variance
Behavior, Animal
Cocaine / administration & dosage*
Conditioning, Operant / drug effects*
Dopamine Uptake Inhibitors / administration & dosage*
Drug Interactions
Motor Activity / drug effects*
Protein Binding / drug effects
Rats, Inbred F344
Rats, Inbred Lew
Self Administration*
Species Specificity
Time Factors
Tropanes / administration & dosage,  pharmacology*
Grant Support
Reg. No./Substance:
0/3beta-(4-chlorophenyl) tropane-2beta-(3-(4'-methylphenyl) isoxazol-5-yl) hydrochloride; 0/Dopamine Uptake Inhibitors; 0/Tropanes; 50-36-2/Cocaine

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