Standard Operating Procedure (SOP) for Combined ICA and Systemic Administration of MPTP: The Overlesioned (Bilateral Asymmetric) Non-human Primate Model

This standard operating procedure (SOP) describes safe methods for the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in non-human primates (adult macaque monkeys). In both humans and nonhuman primates, the administration of MPTP produces a stable Parkinsonian syndrome. Upon entering the brain, MPTP is converted into the toxic metabolite MPP+ by the enzyme monoamine oxidase B (MAO-B). MPP+ accumulates selectively in neurons possessing a dopamine (DA) uptake system and is further concentrated in mitochondria. The basis of the toxic effects of MPP+ is only partially understood; retrograde axonal transport, melanin binding, and damage to the mitochondrial respiratory system have been implicated in the pathogenesis of injury to DA neurons. MPTP administration reproduces in monkeys a syndrome that closely approximates naturally occurring Parkinson’s disease (PD) with respect to the pattern of DA cell loss, the resultant abnormalities in brain physiology, and ultimately, clinical symptoms. This SOP describes the procedures for the combined internal carotid artery (ICA) and systemic (intravenous or intramuscular) administration of MPTP in non-human primates. This model produces an overlesioned or bilateral asymmetric model, induced by unilateral ICA plus systemic administration. This protocol has been adapted from Bankiewicz et al. (1999).