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

  1. 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
  2. Department of Chemistry, SUNY at Buffalo, Buffalo, New York, USA, , , , , , US
    L. Mark Hodges, Melinda M. Hodges & Huw Davies

Authors

  1. D. C. S. Roberts
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  2. Rachel Phelan
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  3. L. Mark Hodges
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  4. Melinda M. Hodges
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  5. Barbara Bennett
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  6. Steve Childers
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  7. 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

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