Nefiracetam has been reported to increase intracellular cyclic AMP levels and enhance calcium channel current. Since the cAMP cascade is involved in the development of drug dependence, we investigated whether nefiracetam attenuates the methamphetamine (MAP)-induced discriminative responses in rats. Nefiracetam (50 mg/kg) inhibited MAP-induced discriminative responses. Furthermore, rolipram, raclopride, and L-745870, all of which can enhance cAMP activity, disrupted MAP-paired lever press of rats. Nifedipine and neomycin, which are blockers of voltage-sensitive calcium channels (VSCCs), decreased MAP-induced discriminative responses. However, pretreatment of these VSCC blockers failed to affect the inhibitory effects of nefiracetam on MAP-induced discriminative responses. Our findings suggested that nefiracetam inhibits MAP-induced discriminative responses, which may be at least partly associated with the changes in intracellular cAMP levels.