Self-administration of cocaine analogs by rats (original) (raw)
Abstract
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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Authors and Affiliations
- Department 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
Authors
- D. C. S. Roberts
You can also search for this author inPubMed Google Scholar - Rachel Phelan
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You can also search for this author inPubMed Google Scholar - Melinda M. Hodges
You can also search for this author inPubMed Google Scholar - Barbara Bennett
You can also search for this author inPubMed Google Scholar - Steve Childers
You can also search for this author inPubMed Google Scholar - Huw Davies
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Received: 29 October 1998 / Final version: 5 February 1999
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Roberts, 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