Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects.
The vigilance-enhancing agent 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. The present study determines the protective effects of modafinil in the marmoset 1-methyl-1,2,3,6-tetrahydropyridine Parkinson model on behavior and on monoamine levels. Twelve marmoset monkeys were treated with a total dose of 6 mg/kg 1-methyl-1,2,3,6-tetrahydropyridine. Simultaneously, six animals received a daily 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 3 weeks. Modafinil largely prevented the 1-methyl-1,2,3,6-tetrahydropyridine-induced change in observed behavior, locomotor activity, hand-eye coordination and small fast movements, whereas the vehicle could not prevent the devastating effects of 1-methyl-1,2,3,6-tetrahydropyridine. Dopamine levels in the striatum of the vehicle+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 5% of control levels, whereas the dopamine levels of the modafinil+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 41% of control levels. The present data suggest that modafinil prevents decrease of movement-related behavior and dopamine levels after 1-methyl-1,2,3,6-tetrahydropyridine intoxication and can be an efficaceous pharmacological intervention in the treatment of Parkinson's disease.
van Vliet
Sanneke A M
SA
Department of Diagnosis and Therapy, TNO Defence, Security and Safety, Rijswijk, The Netherlands. sanneke.vanvliet@tno.nl
Vanwersch
Raymond A P
RA
Jongsma
Marjan J
MJ
van der Gugten
Jan
J
Olivier
Berend
B
Philippens
Ingrid H C H M
IH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002144:Callithrix; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D000077408:Modafinil; D009043:Motor Activity / Q000187:drug effects*; D009048:Motor Skills / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects*
D001559:Benzhydryl Compounds; D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000077408:Modafinil; D004298:Dopamine