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 to better understand how these drugs may be working when administered in combination. The DA uptake inhibitors
GBR 12909 [1-{2-[bis-(4-fluorophenyl)methoxy]-ethyl}-4-(3-phenylpropyl)
piperazine],
WIN 35,428 [2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane],
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 suggest 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.