Methamphetamine (METH) is a highly addictive
drug that might induce neurotoxicity. Clinical trials have reported that
modafinil, a wake-promoting agent used to treat
sleep disorders, may have some efficacy for the treatment of psychostimulant addiction. In this study we tested possible
neuroprotective effects of
modafinil after toxic METH administration in mice. We evaluated the effect of
modafinil (two
injections of either 90 or 180 mg/kg) and METH binge (3 × 7 mg/kg i.p.
injections, 3-h apart) coadministration on DA striatal content, TH immunoreactivity in striatal areas and spontaneous locomotor activity. We also investigated acute locomotor activity and stereotypy profile in mice treated with a single METH dose (2 and 7 mg/kg) pretreated with
modafinil (90 and 180 mg/kg). We found that mice treated with a METH binge showed a marked decrease in DA and dopaminergic metabolites as well as lower levels of TH immunoreactivity in the dorsal striatum. Pretreatment with
modafinil (both 90 and 180 mg/kg) attenuated these effects but did not prevent METH induced decrease in locomotion. We also found that groups that received the combination of both
modafinil and single dose METH showed a decrease in total distance traveled in an open field compared with METH groups. We observed an increment in the time mice expended doing stereotypic movements (continuous sniffing) in the group that received the combination of both METH and
modafinil (i.e., decreasing locomotion). Our results suggest a possible protective role of
modafinil against METH acute striatal toxicity.