Neuroprotective effects of modafinil in a marmoset Parkinson model:
behavioral and neurochemical aspects
by
van Vliet SA, Vanwersch RA, Jongsma MJ,
van der Gugten J, Olivier B, Philippens IH.
^aDepartment of Diagnosis and Therapy,
TNO Defence, Security and Safety, Rijswijk
^bDepartment of Psychopharmacology,
Utrecht Institute of Pharmaceutical Sciences and Rudolf Magnus Institute of Neurosciences,
Utrecht University, Utrecht, The Netherlands.
Behav Pharmacol. 2006 Sep;17(5-6):453-62.

ABSTRACT

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.

Nuvigil
Modafinil: review
Modafinil: structure
Modafinil and serotonin
Modafinil and the marmoset
Excessive daytime sleepiness
Modafinil as an antidepressant
Parkinson's disease: resources
Narcolepsy and sleep disorders: resources

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