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Research ArticleArticle

Effects of the Long-Acting Monoamine Reuptake Inhibitor Indatraline on Cocaine Self-Administration in Rhesus Monkeys

S. Stevens Negus, Michael R. Brandt and Nancy K. Mello
Journal of Pharmacology and Experimental Therapeutics October 1999, 291 (1) 60-69;
S. Stevens Negus
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Michael R. Brandt
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Nancy K. Mello
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Abstract

Cocaine is a nonselective monoamine reuptake inhibitor that is widely abused. Useful pharmacotherapies for cocaine dependence may include substitution medications that produce cocaine-like effects but have a slower onset and longer duration of action. Accordingly, the present study examined the effects of the long-acting, nonselective monoamine reuptake inhibitor indatraline in assays of cocaine discrimination and cocaine self-administration that have been used to evaluate other candidate treatment medications. In rhesus monkeys trained to discriminate cocaine (0.4 mg/kg) from saline, indatraline (0.1–1.0 mg/kg) produced a dose- and time-dependent substitution for cocaine. The effects of 1.0 mg/kg indatraline peaked after 30 min and lasted up to 24 h. In monkeys trained to self-administer 0.032 mg/kg/injection cocaine and food pellets during alternating daily sessions of cocaine and food availability, indatraline (0.0032–0.032 mg/kg/injection) maintained lower rates of responding than cocaine. Repeated treatments with indatraline (0.1–0.56 mg/kg/day) for 7 days produced dose-dependent and sustained decreases in cocaine self-administration across a broad range of cocaine doses (0.0032–0.1 mg/kg/injection), and the highest dose of indatraline (0.56 mg/kg/day) nearly eliminated cocaine-maintained responding. However, doses of indatraline that decreased cocaine self-administration also usually decreased rates of food-maintained responding and produced behavioral stereotypies and trends toward weight loss and mild anemia. These findings suggest that although indatraline may decrease cocaine-taking behavior in rhesus monkeys, it also produces undesirable side effects that may limit its clinical utility in the treatment of cocaine dependence.

Footnotes

  • Send reprint requests to: S. Stevens Negus, Alcohol and Drug Abuse Research Center, Harvard Medical School, McLean Hospital, 115 Mill St., Belmont, MA 02178-9106. E-mail: negus{at}mclean.org

  • ↵1 This work was supported by Grants P50-DA04059, T32-DA07252, and K05-DA00101 from the National Institute on Drug Abuse, National Institutes of Health.

  • Abbreviations:
    FR
    fixed ratio
    VR
    variable ratio
    • Received February 19, 1999.
    • Accepted May 14, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 1
1 Oct 1999
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Research ArticleArticle

Effects of the Long-Acting Monoamine Reuptake Inhibitor Indatraline on Cocaine Self-Administration in Rhesus Monkeys

S. Stevens Negus, Michael R. Brandt and Nancy K. Mello
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 60-69;

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Research ArticleArticle

Effects of the Long-Acting Monoamine Reuptake Inhibitor Indatraline on Cocaine Self-Administration in Rhesus Monkeys

S. Stevens Negus, Michael R. Brandt and Nancy K. Mello
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 60-69;
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