Effects of Modafinil and R-Modafinil on Brain Stimulation Reward Thresholds: Implications for Their Use in the Treatment of Psychostimulant Dependence

Abstract

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 – 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 10 and 20 mg/kg doses. R-modafinil only produced non-significant 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.

Oral modafinil facilitates intracranial self-stimulation in rats: comparison with methylphenidate

“…In support of this possibility, i.p. modafinil was recently shown to facilitate ICSS in rats; however, effects were weak and significant only at 150 mg/kg (Burrows et al, 2015). The higher potency of modafinil administered p.o.…”

R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity

“…There is only a small body of literature referring differences in cognitive and behavior effects between MO and R-MO. Brain reward function indicated by intracranial self-stimulation was reduced by MO at a dose of 150 mg/kg body weight which was not found for R-MO [ 22 ]. Although there are some studies comparing MO and R-MO regarding their wake promoting effects [ 23 ], little is known concerning drug specific effects on cognition.…”

Psychostimulant Use Disorder, an Unmet Therapeutic Goal: Can Modafinil Narrow the Gap?

“…Modafinil has been shown to facilitate ICSS responses in rats when administered orally ( Lazenka and Negus, 2017 ) and intraperitoneally ( Burrows et al, 2015 ). R-MOD shows a trend toward ICSS facilitation at high doses (150 mg/kg) in rats, without reaching significance ( Burrows et al, 2015 ).…”

“…Modafinil has been shown to facilitate ICSS responses in rats when administered orally ( Lazenka and Negus, 2017 ) and intraperitoneally ( Burrows et al, 2015 ). R-MOD shows a trend toward ICSS facilitation at high doses (150 mg/kg) in rats, without reaching significance ( Burrows et al, 2015 ). However, when compared with commonly abused psychostimulants, such as methylphenidate or cocaine, MOD shows significant changes in ICSS rates only when administered at very high doses, while abused drugs show effects at significantly lower doses ( Burrows et al, 2015 ; Lazenka and Negus, 2017 ).…”

“…R-MOD shows a trend toward ICSS facilitation at high doses (150 mg/kg) in rats, without reaching significance ( Burrows et al, 2015 ). However, when compared with commonly abused psychostimulants, such as methylphenidate or cocaine, MOD shows significant changes in ICSS rates only when administered at very high doses, while abused drugs show effects at significantly lower doses ( Burrows et al, 2015 ; Lazenka and Negus, 2017 ). These dose differences may indicate that MOD abuse liability, if any, might require specific conditions, including very high doses, as compared to commonly abused psychostimulants.…”