Behavioral Effects of MPTP Administration in the Vervet Monkey

Abstract

The neurotoxin l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces parkinsonian neurochemical and functional deficits in primates, which may be useful for evaluating the effects of possible antiparkinsonian treatments. Sixty-six adult male vervet monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (0.3–0.4 mg/kg., given 4–5 doses over a 5-day period, cumulative dose 1.6–2.0 mg), and 11 were saline-treated controls. Trained observers recorded spontaneous behaviors twice daily (5 min per observation, 5 × week) for varying periods after MPTP administration. Some behaviors were recorded if they occurred any time during a 5-sec period (e.g., climb, shift, chew) or lasted for a full 5-sec duration (e.g., freeze, immobility). Behaviors were also rated on a scale of 0–5 (e.g., poverty of movement, limb and head tremor) during spontaneous behavior and after “challenges” with food or threats. Individual behaviors were analyzed, and summary factors were calculated reflecting parkinsonian, intention tremor, anxiety, arousal, and healthy behaviors. MPTP administration resulted in behavior not observed in control subjects (i.e., tremor, freezing, immobility, eating problems, delayed and poverty of movement) and reduced healthy, arousal, and anxiety-related behavior. The parkinsonian score, based on factor analysis from the month after treatment, was used to determine and categorize the severity of MPTP deficits and was hypothesized to predict the outcome or stability of the deficit over time.