Self-administration of cocaine analogs by rats

A novel scheme for the synthesis of cocaine analogs from vinylcarbenoid precursors has made available compounds that have a diverse range of affinities for the DA and 5-HT transporters. These compounds were used to explore the relationship between their biochemical properties and their reinforcing e...

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Bibliographic Details
Published in:Psychopharmacologia 1999-06, Vol.144 (4), p.389-397
Main Authors: ROBERTS, D. C. S, PHELAN, R, HODGES, L. M, HODGES, M. M, BENNETT, B, CHILDERS, S, DAVIES, H
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carrier Proteins - drug effects
Cocaine - administration & dosage
Cocaine - analogs & derivatives
Cocaine-Related Disorders - etiology
Dopamine Antagonists - pharmacology
Dopamine Plasma Membrane Transport Proteins
Drug addictions
Male
Medical sciences
Membrane Glycoproteins - drug effects
Membrane Transport Proteins
Nerve Tissue Proteins
Rats
Rats, Wistar
Reinforcement Schedule
Self Administration
Serotonin Plasma Membrane Transport Proteins
Toxicology
Tropanes - administration & dosage
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Summary:A novel scheme for the synthesis of cocaine analogs from vinylcarbenoid precursors has made available compounds that have a diverse range of affinities for the DA and 5-HT transporters. These compounds were used to explore the relationship between their biochemical properties and their reinforcing effects. The objective was to assess the reinforcing efficacy of selected cocaine analogs and compare the results with their selectivity in binding to DA and 5-HT transporters. Rats were prepared with chronically indwelling intravenous cannulae and trained to self-administer cocaine on a progressive ratio (PR) schedule. A range of doses of seven cocaine analogs were substituted for cocaine in separate groups of animals. The results demonstrate a wide range of reinforcing efficacies and potencies among the seven selected drugs. Four tropane analogs (WF-11, WF-23, WF-24, WF-55) were found to support self-administration behavior on a PR schedule while three did not (WF-31, WF-54 and WF-60). The DA/5-HT selectivity ratio was found to be a better predictor of self-administration behavior than affinity at the DA transporter alone. These data suggest that drugs with a higher affinity for the DA versus the 5-HT transporter are more likely to be self-administered.
ISSN:0033-3158
1432-2072
DOI:10.1007/s002130051022