Cocaine discrimination: relationship to local anesthetics and monoamine uptake inhibitors in C57BL/6 mice

Although the discriminative properties of cocaine have been examined extensively in rats, and to a lesser extent in other species, there are currently no reports on cocaine discrimination by mice. In one of our experiments, C57BL/6 (C57) mice acquired cocaine discrimination (10 mg/kg training dose) and exhibited dose responsive generalization to lower doses of the drug, which was similar to previous reports using rats. In addition, mazindol, a general monoamine uptake inhibitor similar to cocaine, and nomifensine, which is relatively specific for the dopamine transporter, substituted completely for cocaine, as described for rats. In contrast, there was little substitution evidenced by monoamine uptake inhibitors relatively specific for the norepinephrine transporter (nisoxetine) or for the serotonin transporter (fluoxetine), or by the local anesthetics procaine or lidocaine. In our second experiment, neither cocaine nor mazindol substituted for procaine in animals trained to discriminate the local anesthetic (100 mg/kg) although lidocaine substituted completely for the procaine cue. These experiments emphasize the importance of the dopamine transporter in mediating the discriminative stimulus effects of cocaine in C57 mice. The lack of cross generalization between cocaine and procaine suggests that the anesthetic properties of cocaine contribute little toward its discrimination by this mouse strain.