EVALUATION OF THE COCAINE LIKE DISCRIMINATIVE STIMULUS EFFECTS AND REINFORCING EFFECTS OF MODAFINIL

Modafinil [(diphenyl-methyl)sulphinyl-2-acetamide] is a novel psychost imulant drug which is effective in the treatment of narcolepsy and idi opathic hypersomnia. It also has neuroprotective effects in animal mod els of striatal neuropathology. Although the cellular mechanisms of ac tion of modafinil are poorly understood, it has been shown to have a p rofile of phar macological effects that differs considerably from that of amphetamine-like stimulants. There is some evidence that modafinil has central alpha(1)-adrenergic agonist effects. In the present study modafinil was evaluated for cocaine-like discriminative stimulus effe cts in rats and for reinforcing effects in rhesus monkeys maintained o n intravenous cocaine self-administration. Modafinil, l-ephectrine and d-amphetamine all produced dose dependent increases in cocaine-lever responding, with maximal levels of 67%, 82% and 100%, respectively. Mo dafinil produced full substitution in four out of the six rats tested while the highest levels of substitution were associated with substant ial response rate decreasing effects. Little evidence was obtained tha t the discriminative stimulus effects of modafinil were produced by al pha(1)-adrenergic activation, based upon results of tests performed in combination with prazosin. In the self-administration procedure, moda finil and l-ephedrine functioned as reinforcers in rhesus monkeys. The reinforcing and discriminative stimulus effects of modafinil required very high doses: modafinil was over 200 times less potent than d-amph etamine and was also less potent than d-ephedrine. These results show that modafinil has some cocaine-like discriminative stimulus effects a nd, like other abused stimulants, can serve as a reinforcer at high do ses.