INTRODUCTION to Parkinson’s Disease:

Parkinson’s disease (PD) is a neurodegenerative movement disorder that afflicts over half a million people in the United States, most of them senior citizens. Each year, about 50,000 new cases are diagnosed; and this may under-represent PD prevalence since symptoms develop so gradually. Victims progressively deteriorate in terms of coordination and movement, and may experience tremors, mental deterioration and dementia, muscle rigidity, and loss of the ability to walk, speak, or perform other activities. The disorder results from the loss of dopaminergic neurons, although the exact cause for this deterioration is as of yet undetermined. There are several methods of treatment for PD, but there is currently no cure (Isacson, 1996; Rajput et al., 1984).

Animal models of PD allow researchers to study the pathology of PD while tracking physical and behavioral changes during the entire disease course. Due to compensatory mechanisms, human PD symptoms usually do not show up until more than 80% of striatal dopamine (DA) levels are depleted, making it difficult to study the onset and earliest stages of the disease in humans (Hornykiewicz, 1993). Moreover, parkinsonian symptoms appear in several other human disorders, leading to a misdiagnosis rate of about 24% (Lang & Lozano, 1998). Animal models designed to simulate PD eliminate these problems, making them a useful tool for understanding and treating PD (Betarbet, Sherer, & Greenamyre, 2002; Deumens, Blokland, & Prickaerts, 2002; Beal, 2001; Zigmond & Stricker, 1984).

BACKGROUND of model:

Urban Ungerstedt developed the rat 6-OHDA unilateral-lesion model of Parkinson’s disease, which can be used to model hemi-parkinsonian symptoms, early stages of PD when one hemisphere deteriorates more rapidly than the other, and acute catecholaminergic neuron loss. It offers easily quantifiable behavior and a short time course, making it an efficient model for testing drugs that act on DAergic neurons and DA receptors. Rats with unilateral lesions to the substantia nigra (SN) rotate in response to apomorphine, d-amphetamine, and other dopaminergic receptor agonists. Several studies have found that the number of rotations correlates with DA denervation. Currently there is no method of predicting the amount of rotation that will occur with different amounts of damage, which makes it difficult for researchers to quantify the efficacy of experimental PD treatments. Thus our project sought to synthesize existing rotational data and determine a mathematical equation that fit with experimental observations, in order to more fully charactarize the nature of the 6-OHDA model.

SURGERY: You are going to perform a virtual experiment using the unilateral 6-OHDA model. Your rats will be given neurotoxic 6-OHDA injections to the substantia nigra of the right hemisphere. The toxin will selectively destroy dopaminergic neurons beginning within 24 hours, leading to Parkinson-like symptoms. You will select the amount of denervation you would like to induce, choose a drug with which to challenge your animals, and view graphs of the rats' rotational behavior both pre- and post- lesion. To proceed to the simulation, click here.

For a one-semester lab-based course in behavioral neuroscience, interactive 6-OHDA wetlab CDs are available for institutional purchase by contacting juramirez@davidson.edu