Received for publication December 27, 2005.
Revised February 10, 2006.
Accepted for publication February 13, 2006.

Interactions of Cocaine with Dopamine Uptake Inhibitors or Dopamine Releasers in Rats Discriminating Cocaine

Abstract

Several dopamine (DA) indirect agonists have been proposed as potential medications for treating cocaine abuse. The objective of the present study was to quantify the interactions among cocaine and DA uptake inhibitors or DA releasers in order to better understand how these drugs may be working when administered in combination. The DA uptake inhibitors GBR 12909, WIN 35,428, methylphenidate, indatraline, nomifensine and mazindol, and DA releasers methamphetamine, d-amphetamine, methcathinone, cathinone, fencamfamine and phentermine were examined alone and in combination with cocaine in rats trained to discriminate cocaine (10 mg/kg, i.p.) from saline injections. All of the DA indirect agonists dose-dependently substituted for cocaine, and shifted the cocaine dose-effect curve leftward. Isobolographic analysis indicated the interactions were generally additive, although both methamphetamine and d-amphetamine were quantitatively determined to be more potent than DA uptake inhibitors in shifting the cocaine dose-effect function to the left. The potential of d-amphetamine as an effective treatment for cocaine abuse, and negative clinical results with dopamine uptake inhibitors suggests that differences in shifts in dose-effect curves should be further examined with emerging clinical data as a predictive index of potential treatments for cocaine abuse.

Key words: Additive, Cocaine, DA Releasers, Drug Discrimination, Potentiation, Uptake Inhibitors