Cocaethylene produces discriminative stimulus properties in the rat: effect of cocaine and ethanol coadministration

Experimentally naive Sprague-Dawley male rats were trained to discriminate the interoceptive stimulus cues produced by either 10.0 mg/kg cocaine or 10.0 mg/kg cocaethylene from their saline vehicles. Although it required more sessions to train the cocaethylene rats, once they were trained to criterion performance the ED50 value for cocaethylene (2.89 mg/kg) was very similar to that of cocaine (3.04 mg/kg). Coadministration of a 300-mg/kg dose of ethanol that produced saline-like responding in cocaethylene-trained rats with 2.5 mg/kg cocaine allowed for 88.9% of first lever selections being made on the cocaethylene-appropriate lever. Time-course evidence using coadministered (1.25-mg/kg) cocaine and (300-mg/kg) ethanol indicated that the formation of cocaethylene was highest, as indicated by discriminative performance, at 15 min and progressively decreased as the postinjection interval was increased to 30, 60, and 120 min. The results are discussed in light of rapid formation of cocaethylene from cotreatment with ethanol and cocaine in the mouse, rat, and human subject. The suggestion is made as to the prevalent, and growing, use of this drug combination in the human population of cocaine abusers.