Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.
Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals.
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
Christopher S
CS
Tallarida
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
Erin
E
Egan
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
Gissel D
GD
Alejo
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA.
Robert
R
Raffa
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
Ronald J
RJ
Tallarida
Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA. Electronic address: scott.rawls@temple.edu.
Scott M
SM
Rawls
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders; D003214:Conditioning, Classical / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004340:Drug Contamination; D004357:Drug Synergism; D013287:Illicit Drugs / Q000494:pharmacology*; D007978:Levamisole / Q000494:pharmacology*; D010932:Planarians; D013028:Space Perception / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects
D018765:Dopamine Uptake Inhibitors; D013287:Illicit Drugs; D007978:Levamisole; D003042:Cocaine
Addiction; Cocaine; Conditioned place preference; Levamisole; Planarians; Psychostimulant; Stereotypy; Synergy