Cocaine and local anesthetics: stimulant activity in rats with nigral lesions

Cocaine and several other local anesthetics were tested for their ability to induce rotational behavior in rats with unilateral 6-hydroxydopamine lesions of substantia nigra. Acute administration of bupivacaine, chloroprocaine, etidocaine, lidocaine, mepivacaine, procaine or tetracaine failed to induce active rotation in this sensitive assay of dopamine agonist activity. On the other hand, cocaine or dimethocaine treatment induced active rotation directed ipsilaterally to the lesioned side, indicating indirect dopamine agonist activity. Repeated administration of cocaine or dimethocaine at 1-week intervals resulted in increased rotational response (i.e., sensitization) while there was no suggestion of sensitization or induction of rotational behavior after weekly repeated administration of procaine or tetracaine. Daily administration of mepivacaine, procaine or tetracaine for 5 days also failed to induce rotation. Dimethocaine thus was found similar to cocaine and different from the other local anesthetics tested both in terms of frank stimulant activity and development of sensitization upon repeated administration.