Effects of modafinil and R-modafinil on brain stimulation reward thresholds: Implications for their use in the treatment of psychostimulant dependence

Background. Modafinil and its enantiomer R-modafinil are approved for the treatment of various sleep disorders, and may also be efficacious in the treatment of psychostimulant abuse. However, the ability of modafinil and R-modafinil to alter brain reward function has not yet been assessed. Purpose. This study assessed the effects of modafinil and R-modafinil on brain reward function using the intracranial self-stimulation (ICSS) paradigm. Study design. Male Sprague-Dawley rats were trained to respond for ICSS using current-intensity threshold determination procedures. Changes in ICSS thresholds were then assessed following administration of modafinil and R-modafinil (50, 100, and 150 mg/kg), or cocaine (2.5 mg/kg-20 mg/kg) as a positive control. Results. ICSS thresholds were reduced by modafinil at the 150 mg/kg dose, as well as by cocaine at the 10mg/kg and 20mg/kg doses. R-modafinil only produced nonsignificant trends towards reducing ICSS thresholds. Conclusion. Modafinil and R-modafinil have limited effects on brain reward function in otherwise drug-naïve subjects. Additional assessments of these effects in the context of psychostimulant dependence are needed.