Quantitative evaluation of MPTP-treated nonhuman parkinsonian primates in the HALLWAY task

Parkinson's disease (PD) is a progressive neurodegenerative disorder. An experimental model of this disease is produced in nonhuman primates by the administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this work, we put forward a new quantitative evaluation method that uses video recordings to measure the displacement, gate, gross and fine motor performance of freely moving subjects. Four Vervet monkeys (Cercopithecus aethiops) were trained in a behavioral observation hallway while being recorded with digital video cameras from four different angles. After MPTP intoxication the animals were tested without any drug and after 30 and 90 min of Levodopa/Carbidopa administration. Using a personal computer the following behaviors were measured and evaluated from the video recordings: displacement time across the hallway, reaching time towards rewards, ingestion time, number of attempts to obtain rewards, number of rewards obtained, and level of the highest shelf reached for rewards. Our results show that there was an overall behavioral deterioration after MPTP administration and an overall improvement after Levodopa/Carbidopa treatment. This demonstrates that the HALLWAY task is a sensitive and objective method that allows detailed behavioral evaluation of freely moving monkeys in the MPTP Parkinson's disease model.

[1]  R. Ridley,et al.  Continuous Low-Level Glial Cell Line-Derived Neurotrophic Factor Delivery Using Recombinant Adeno-Associated Viral Vectors Provides Neuroprotection and Induces Behavioral Recovery in a Primate Model of Parkinson's Disease , 2005, The Journal of Neuroscience.

[2]  R. Roth,et al.  Upregulation of striatal D2 receptors in the MPTP-treated vervet monkey is reversed by grafts of fetal ventral mesencephalon: an autoradiographic study , 1998, Brain Research.

[3]  M. Herrero,et al.  Measurement of motor disability in MPTP-treated macaques using a telemetry system for estimating circadian motor activity , 2004, Journal of Neuroscience Methods.

[4]  Juan Fernández-Ruiz,et al.  Spatial memory improvement by levodopa in parkinsonian MPTP-treated monkeys , 1999, Psychopharmacology.

[5]  L. Grégoire,et al.  Effect of a selective glutamate antagonist on l-dopa-induced dyskinesias in drug-naive parkinsonian monkeys , 2004, Neurobiology of Disease.

[6]  R. Roth,et al.  Symptomatic and asymptomatic 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreated primates: Biochemical changes in striatal regions , 1989, Neuroscience.

[7]  D. Calne,et al.  Evidence for environmental causation of Parkinson's disease. , 2002, Parkinsonism & related disorders.

[8]  E. Bézard,et al.  Comparison of eight clinical rating scales used for the assessment of MPTP-induced parkinsonism in the Macaque monkey , 2000, Journal of Neuroscience Methods.

[9]  A. Cañas,et al.  Principios de neurología , 1984 .

[10]  C. Schnell,et al.  Cardiovascular parameters telemetrically measured during pregnancy, parturition, and lactation in a common marmoset (Callithrix jacchus). , 2000, Contemporary topics in laboratory animal science.

[11]  W. Le,et al.  Mutant genes responsible for Parkinson's disease. , 2004, Current opinion in pharmacology.

[12]  M. Linnoila,et al.  CSF 5-HIAA and Nighttime Activity in Free-Ranging Primates , 2000, Neuropsychopharmacology.

[13]  I. Horii,et al.  Development of telemetry system in the common marmoset--cardiovascular effects of astemizole and nicardipine. , 2002, The Journal of toxicological sciences.

[14]  J. López-Barneo,et al.  Recovery of Chronic Parkinsonian Monkeys by Autotransplants of Carotid Body Cell Aggregates into Putamen , 1999, Neuron.

[15]  G. Petzinger,et al.  The parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP): a technical review of its utility and safety , 2001, Journal of neurochemistry.

[16]  Filippo Aureli,et al.  Heart rate responses to social interactions in free-moving rhesus macaques (Macaca mulatta): a pilot study. , 1999, Journal of comparative psychology.

[17]  Ian Q Whishaw,et al.  Complete locomotor recovery following corticospinal tract lesions: measurement of ground reaction forces during overground locomotion in rats , 1999, Behavioural Brain Research.

[18]  C. Marsden,et al.  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the common marmoset , 1984, Neuroscience Letters.

[19]  C. Fuller,et al.  Circadian control of thermoregulation in the squirrel monkey, Saimiri sciureus. , 1979, The American journal of physiology.

[20]  H. Pakkenberg,et al.  The clinical syndrome of striatal dopamine deficiency. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). , 1985, The New England journal of medicine.

[21]  T. Aigner,et al.  Long-term cognitive impairment in MPTP-treated Rhesus monkeys , 1995, Neuroreport.

[22]  J. Langston,et al.  Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. , 1983, Science.

[23]  R. Roth,et al.  Severe long-term 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the vervet monkey (Cercopithecus aethiops sabaeus) , 1997, Neuroscience.

[24]  T. Paolo,et al.  Long-term effects of MPTP on central and peripheral catecholamine and indoleamine concentrations in monkeys , 1986, Brain Research.

[25]  A Eschalier,et al.  Assessment of motor behavior using a video system and a clinical rating scale in parkinsonian monkeys lesioned by MPTP , 2001, Journal of Neuroscience Methods.

[26]  A. Imperato,et al.  The Antioxidant Ebselen Prevents Neurotoxicity and Clinical Symptoms in a Primate Model of Parkinson's Disease , 2000, Experimental Neurology.

[27]  R. Roth,et al.  Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys. , 1995, Cell transplantation.

[28]  C. Rebert,et al.  Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey , 1984, Brain Research.

[29]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[30]  M. Matsumura,et al.  Behavioral recovery in a primate model of Parkinson's disease by triple transduction of striatal cells with adeno-associated viral vectors expressing dopamine-synthesizing enzymes. , 2002, Human gene therapy.

[31]  C. Marsden,et al.  Repeated administration of N-methyl-4-phenyl 1,2,5,6-tetrahydropyridine to rats is not toxic to striatal dopamine neurones. , 1984, Biochemical pharmacology.

[32]  P. Blanchet,et al.  Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABAA/benzodiazepine receptor complex and GABA content , 1999, Neurochemistry International.

[33]  M. Hoehn,et al.  Parkinsonism , 1967, Neurology.