Rationale: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: These data suggest that drugs with a higher affinity for the DA versus the 5-HT transporter are more likely to be self-administered.
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Similar content being viewed by others Explore related subjectsDiscover the latest articles and news from researchers in related subjects, suggested using machine learning. Author information Authors and AffiliationsDepartment of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA e-mail: dcsrobts@wfubmc.edu Fax: +1-336-716-8501, , , , , , US
D. C. S. Roberts, Rachel Phelan, Barbara Bennett & Steve Childers
Department of Chemistry, SUNY at Buffalo, Buffalo, New York, USA, , , , , , US
L. Mark Hodges, Melinda M. Hodges & Huw Davies
Received: 29 October 1998 / Final version: 5 February 1999
About this article Cite this articleRoberts, D., Phelan, R., Hodges, L. et al. Self-administration of cocaine analogs by rats. Psychopharmacology 144, 389–397 (1999). https://doi.org/10.1007/s002130051022
Issue Date: June 1999
DOI: https://doi.org/10.1007/s002130051022
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