Repeated administration of cocaethylene induces context-dependent sensitization to its locomotor effects

The cocaine analog, cocaethylene, has recently been identified as an active metabolite in humans consuming ethanol and cocaine. Since this compound exhibits affinity for the dopamine transporter that is more selective than that of cocaine, it is conceivable that its behavioral properties may be distinguishable from those of cocaine (cf. Elsworth et al. 1993). To investigate further the behavioral effects of cocaethylene, its ability to induce sensitization to locomotor activity in C57BL/6 mice was determined and compared with that of cocaine. In the first part of the study, mice were treated repeatedly with cocaethylene in the test environment and were then challenged with several different doses of the same drug. Repeated administration of 10, 20 or 40 mg/kg cocaethylene (IP) for 3 consecutive days produced leftward and upward shifts of the cocaethylene (2.5-56.6 mg/kg, IP) dose-effect curve on day 4. In the second part of the study, mice were treated with 20 mg/kg cocaethylene for 3 days, but were immediately placed back in their home cage following the injection: repeated administration of cocaethylene for 3 consecutive days did not significantly affect the dose-effect curve of cocaethylene (2.5-40 mg/kg, IP) on day 4. In the same paradigm, repeated administration of 20 mg/kg cocaine for 3 consecutive days produced a significant leftward shift of the cocaine (2.5-56.6 mg/kg, IP) dose-effect curve on day 4. These results confirm that cocaethylene shares a number of properties with cocaine, but also suggest that the drugs are not identical.