Behavioral pharmacology of local anesthetics: Reinforcing and discriminative stimulus effects

The reinforcing properties of several short-acting esteratic local anesthetics were determined in rhesus monkeys experienced in the IV self-administration of cocaine. In addition, the discriminative stimulus properties of these and several other local anesthetics of both the ester and amide class were determined in rats trained to discriminate procaine from saline in a 2-lever operant task. IV delivery of chloroprocaine, dimethylprocaine or dimethocaine maintained responding above vehicle levels in most monkeys while propoxycaine, piperocaine and dimethylaminoethanol (Deanol) failed to maintain self-administration behavior. Thus some, but not all, short-acting esteratic local anesthetics are positive reinforcers in rhesus monkeys. In addition, it is unlikely that the reinforcing effects of dimethylprocaine are mediated by its metabolite dimethylaminoethanol. In rats, all local anesthetics tested except piperocaine and procainamide resulted in responding on the procaine-appropriate lever indicating procaine-like discriminative stimulus effects for these compounds. In addition, injections of d-amphetamine resulted in principally procaine lever responding. All local anesthetics that were self-administered by rhesus monkeys had discriminative stimulus effects in rats that were similar to those of procaine. However, not all local anesthetics that were procaine-like in rats were self-administered by rhesus monkeys. These data may represent a separation of these two stimulus properties for local anesthetics although other variables such as species differences may play a role.