Study of the addictive potential of modafinil in naive and cocaine-experienced rats

Rationale: Modafinil is a drug that promotes wakefulness and, as such, is used to treat hypersomnia and narcolepsy. Preclinical and clinical studies suggest that modafinil could possess weak reinforcing effects in drug-experienced subjects. However, its abuse potential in drug-naive healthy individuals is still totally uninvestigated, despite the fact that availability of modafinil has recently increased. Objectives: The purpose of our study was to investigate the potential addictive properties of modafinil by testing its reinforcing effects in naive rats. The interactions of modafinil with the reinforcing effects of cocaine were also tested. Methods: First, using i.v. self-administration and place conditioning tests, we studied the reinforcing and rewarding effects of a large range of doses of modafinil in naive rats. Second, we tested the influence of modafinil on reinforcing and incentive effects of cocaine in rats trained for cocaine self-administration. The effects of modafinil were compared with those of amphetamine and haloperidol. Results: Modafinil did not produce reinforcing or rewarding effects and did not modify the effects of cocaine. Conclusions: Our results suggest that modafinil does not possess an addictive potential in naive individuals. Furthermore, it would be behaviorally distinct from classical central nervous system stimulants which are known to alter cocaine-induced effects. However, as shown previously in nonhuman primates and in humans, modafinil could possibly have reinforcing effects in cocaine-experienced individuals.