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

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.

Sensorimotor rhythm neurofeedback as adjunct therapy for Parkinson's disease

“…Future studies should address the impact of the selected frequency band (here 12–17 Hz) to demonstrate SMR specificity and help elucidate the role of controversially discussed basal ganglia‐thalamocortical rhythms 20, 21, 22, 23, 24. We showed that SMR neurofeedback reduced monkeys’ heart rate close to anesthesia levels (206–245 beats/min)25 and improved HTT mood scores,16 in accordance with findings in normal humans 10…”

“…average of 4 subsequent pre‐study days). Before noon monkeys’ emotional mood was assessed with the Human Threat Test (HTT)16 before (baseline), three times during the training phase and five times during L‐DOPA treatment. Baseline was set to 100%.…”

“…Baseline was set to 100%. For HTT, during a two‐minute period monkeys’ postures and jumps were scored as fear related or relaxed and expressed as ratio between number of relaxed postures and jumps relative to total number 16. All observations were made by two cross‐validated blinded technicians.…”

“…Dopamine positive neurons of the Substantia nigra pars compacta (SNpc) were counted with tyrosine hydroxylase immune reactive (TH‐IR) staining by a blinded technician 15, 16…”

Neuroprotective Effects of Delta-9-Tetrahydrocannabinol in a Marmoset Parkinson Model

“…These markers are sensitive to reflect neurodegeneration and neuroprotection in the MPTP marmoset model [24]. The parkinsonian symptoms are assessed by using two extensive behavioral observation scales for PD and functional tests measuring locomotor activity and hand-eye coordination (HEC) [25,26].…”