Document Detail


Stimulation of 5-HT(1B) receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior.
MedLine Citation:
PMID:  19650818     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paradoxically, stimulation of 5-HT(1B) receptors (5-HT(1B)Rs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT(1B)R agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3-10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0-1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT(1B)Rs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT(1B)Rs may be a novel target for developing medications for cocaine dependence.
Authors:
Nathan S Pentkowski; Jazmin I Acosta; Jenny R Browning; Elizabeth C Hamilton; Janet L Neisewander
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-07-24
Journal Detail:
Title:  Addiction biology     Volume:  14     ISSN:  1369-1600     ISO Abbreviation:  Addict Biol     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-10     Completed Date:  2010-03-10     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  9604935     Medline TA:  Addict Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  419-30     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal*
Cocaine / administration & dosage,  pharmacology*
Cocaine-Related Disorders / metabolism*,  prevention & control*
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Schedule
Extinction, Psychological
Hallucinogens / pharmacology*
Male
Motivation / drug effects*
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT1B / drug effects*
Reinforcement (Psychology)*
Sucrose / administration & dosage
Sweetening Agents / administration & dosage
Grant Support
ID/Acronym/Agency:
DA11064/DA/NIDA NIH HHS; R01 DA011064/DA/NIDA NIH HHS; R01 DA011064-10A1/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Hallucinogens; 0/Receptor, Serotonin, 5-HT1B; 0/Sweetening Agents; 57-50-1/Sucrose; I5Y540LHVR/Cocaine
Comments/Corrections

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


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