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Spermine interacts with cocaine binding sites on dopamine transporters

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Abstract

These studies were designed to assess the potential interaction of the polyamine spermine with cocaine binding to dopamine and serotonin transporters. The results of the experiments presented here indicate that spermine inhibits binding of the cocaine congener [3H] CFT to striatal synaptosomal membranes. Further, although [3H] CFT is known to interact with both dopamine and serotonin transporters, our results indicate that the observed inhibition of [3H] CFT binding is likely to reflect a specific inhibition of binding to dopamine transporters. Spermine significantly inhibited the binding of both [3H] CFT and [3H] mazindol to dopamine transporters, while it had no apparent effects on the binding of the potent serotonin uptake inhibitor [3H] paroxetine. Finally, saturation experiments show that the inhibition of ligand binding to the cocaine binding site on dopamine transporters appears not to be due to a modification of ligand affinity for the transporter, but to a decrease in the apparent density of ligand binding sites. The results of these experiments indicate that endogenously produced polyamines can alter cocaine binding to the dopamine transporter. The results are discussed in terms of possible impact on novel approaches for pharmacologically manipulating cocaine reinforcement and craving in clinical treatments for cocaine addiction, as well as for emergency treatment of cocaine overdose.

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Authors and Affiliations

  1. Center on Alcoholism, Substance Abuse and Addictions and Departments of Psychiatry and Psychology, University of New Mexico, 87131, Albuquerque, NM, USA

    Mary C. Ritz

  2. Section on Neuroimaging and Drug Action, Neuroscience Branch, Addiction Research Center, National Institute on Drug Abuse, PO Box 5180, 21224, Baltimore, MD, USA

    Charles R. Mantione & Edythe D. London

Authors
  1. Mary C. Ritz
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  2. Charles R. Mantione
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  3. Edythe D. London
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Ritz, M.C., Mantione, C.R. & London, E.D. Spermine interacts with cocaine binding sites on dopamine transporters. Psychopharmacology 114, 47–52 (1994). https://doi.org/10.1007/BF02245443

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