Introduction

Degeneration of dopaminergic neurons in the substantia nigra is a hallmark of Parkinson's disease (PD). However, despite decades of research, the cause of PD and the underlying mechanism of action responsible for the progressive degeneration of nigral dopaminergic neurons remain poorly understood (1). The creation of rodent and primate models for PD has provided a valuable tool in the study of the pathogenetic progression of the disease (2). On the other hand, primary neural cell cultures have...

The Acute and Subacute Mouse MPTP Model

To induce a robust depletion of striatal DA in mice, large doses of MPTP and frequent injections are required. In mouse studies, MPTP is commonly administered either by an acute or subacute regimen. The acute MPTP studies generally follow the model that was initially examined by Sonsalla and Heikkila (38), who injected mice four times with 20 mg kg of MPTP at 1- or 2-hr intervals within a day. With this acute model, it was indicated that most mice do not survive after three or more injections...

The Chronic Mouse MPTPProbenecid Model

Pharmacokinetic consideration could be one of the underlying reasons why acute and subacute MPTP injections do not produce a sustained neurological insult in laboratory animals. It has been established that MPTP in rodents, following its peripheral administration, is rapidly excreted through the kidney (62). After reaching the central nervous system (CNS), this toxin and its active metabolite, MPP+, are quickly cleared from the brain (63). Hence, investigators tend to intensify MPTP...