Featured Paper of the Month – October 2020.
Modafinil and methylphenidate are clinically available medications that inhibit the reuptake of dopamine in neurons, a common mechanism with psychostimulants like cocaine. We investigated the reinforcing actions of modafinil or methylphenidate alone and in combination with cocaine, in rats. While rats did not self-administer modafinil, suggesting low abuse liability, methylphenidate was self-administered similarly to cocaine. However, while both drugs potentiated cocaine’s reinforcing effects, only methylphenidate potentiated the elevated dopamine levels produced by cocaine. In contrast to methylphenidate, the effects of modafinil were attenuated by the gap-junction inhibitor carbenoxolone. Our results suggest that modafinil shares common mechanisms with cocaine and methylphenidate, but has a unique pharmacological profile that includes lower abuse liability and facilitation of electrotonic coupling that may be related to its effectiveness in subpopulations of cocaine abusers. These findings may be exploited in future therapeutic drug design for treatment of cocaine use disorder.
Neuropsychopharmacology, 45 (9), pp. 1518–1526, 2020, ISBN: 1740-634X.