Effect of melatonin on cocaine-induced behavioral sensitization.

Melatonin, a pineal hormone and a potent free radical scavenger with neuroprotective actions, has been reported to act as an inhibitor of nitric oxide synthase (NOS). We have earlier shown that inhibitors of NOS (N(omega)-nitro-L-arginine methyl ester [L-NAME], 7-nitroindazole [7-NI]) block cocaine-induced behavioral sensitization. In the present study, the effects of melatonin on cocaine behavior were studied. A single injection of melatonin markedly augmented cocaine-induced locomotor activity. Rats injected daily with melatonin prior to cocaine injections failed to elicit cocaine sensitization. These behavioral effects of melatonin do not completely mimic those of other NOS inhibitors, suggesting that the effects of melatonin on cocaine behavior are mediated by both NOS-dependent as well as NOS-independent mechanisms.