Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects

Sanneke A.M. van Vliet, Raymond A.P. Vanwersch, Marjan J. Jongsma, Jan van der Gugten, Berend Olivier, Ingrid H.C.H.M. Philippens
2006 Behavioural Pharmacology  
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
more » ... 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).
doi:10.1097/00008877-200609000-00011 pmid:16940766 fatcat:5wtlvz727bhkfk6saerfhyvwhy