The effects of concurrent administration of +/-3,4-methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat

Abstract

Conditioned place preference (CPP), a commonly used model for studying the role of contextual cues in drug reward and drug seeking, was employed to explore possible behavioral interactions between (+/-)3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") and cocaine. On each of four occasions, adult male rats received one of three doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg; administered subcutaneously [s.c.]) combined with one of three doses of cocaine (0 mg/kg, 2.5 mg/kg, 5 mg/kg; administered intraperitoneally [i.p.]), and were then tested in a CPP paradigm. The results showed MDMA-induced CPP at a unit dose of 5 mg/kg, but at the 10 mg/kg dose there was a return to baseline (control) performance levels. For cocaine alone, CPP increased in a linear fashion as the drug dose was increased. Concurrent administration resulted in antagonism of each drug, but there was evidence that this pattern was reversible at higher doses of the respective drugs. These data are instructive insofar as they suggest that the behavioral and neurochemical effects of MDMA and cocaine presented in isolation are dramatically altered when the two drugs are presented in combination.

Figure 1. Cocaine and MDMA effects

Mean (±SEM) CPP conditioning scores (measured in min) for animals exposed to 0 mg/kg, 2.5 mg/kg, or 5 mg/kg cocaine (COC) across doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg). Groups not possessing a common letter were significantly different (p<0.05).