Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects
The psychostimulant modafinil has neuroprotective properties: it prevents striatal ischemic injury, nigrostriatal pathway deterioration after partial transsection and intoxication with 1-methyl-1,2,3,6-tetrahydropyridine (MPTP). The present study determines the protective effects of modafinil in the marmoset MPTP Parkinson model on behavior and on monoamine levels. Twelve marmoset monkeys were treated with a total dose of 6 mg/kg MPTP. Simultaneously, six animals received a daily oral dose of
... aily oral dose of modafinil (100 mg/kg) and six animals received vehicle for 27 days. Behavior was observed daily and the locomotor activity, hand-eye coordination, small fast movements, anxiety-related behavior and startle response of the animals were tested twice a week for three weeks. Modafinil largely prevented the MPTP-induced change in observed behavior, locomotor activity, hand-eye coordination and small fast movements, whereas the vehicle could not prevent the devastating effects of MPTP. Dopamine (DA) levels in the striatum of the vehicle + MPTP treated animals were reduced to 5% of control levels, whereas the DA levels of the modafinil + MPTP treated animals were reduced to 41% of control levels. The present data suggest that modafinil prevents decrease of movement-related behavior and DA levels after MPTP intoxication and can be a potent pharmacological intervention in the treatment of Parkinson's disease (PD).