Rotational Behavior During the Pole Test: A Novel Behavioral Assay in a Mouse Model of Parkinson's Disease
Abstract
Parkinson’s disease (PD) is a debilitating disorder that is likely to reach pandemic proportions by the year 2040, and there is no cure. Current treatments are symptomatic in nature and often have deleterious side effects, such as L-dopa-induced dyskinesia. Neuroprotective drugs, however, target the cause of PD, which is neuronal death; these drugs may prevent motor deficits from progressing in patients with PD. The development of neuroprotective drugs, however, requires a reliable and clinically translatable animal model for PD. The classic preclinical model for testing drugs for PD is a rodent model based on intracranial injections of 6-hydroxydopamine (6-OHDA), a neurotoxin that results in the loss of dopaminergic neurons. Injection of 6-OHDA into the dorsolateral striatum of rodents results in retrograde degeneration of dopaminergic axons, resulting in the loss of dopaminergic neuronal cell bodies within the substantia nigra pars compacta (SNc), which is the brain region lost in PD. Unilateral lesioning with 6-OHDA damages only one side of the SNc, and the extent of damage can be quantified with drug-induced rotational assays. These behavioral assays, while effective, require administration of additional drugs to induce rotations. The use of drugs, specifically apomorphine or amphetamine, to induce rotations in 6-OHDA injected rodents is problematic because of potential drug-drug interactions, especially in the setting of drug discovery. To address this issue, I developed a new behavioral assay that induces rotational behavior during a motor task without the need for additional drugs. I utilized either sham-operated or ovariectomized female mice that were injected with 6-OHDA into the dorsolateral striatum. These mice were subjected to a specialized task in which the mice were required to turn and descend down a 2-foot pole. Three trials per mouse were conducted at 5 time points, which included 2 time points prior to 6-OHDA injection and 3 time points following 6-OHDA injection; each time point was at least one week apart. I quantified several parameters utilizing this assay format, including the time to turn, time to descend, average score of descent, direction of rotations, and number of rotations. Results showed that 6-OHDA significantly increased the number of rotations in both ovariectomized and sham-operated female mice without the use of any additional drug. My data suggest that spontaneous rotations whilst performing a specialized task such as descent down a 2-foot pole are a useful measure for the discovery of preclinical neuroprotective drugs to treat PD.
Subject
Parkinson's diseaseneuroprotective drugs
6-OHDA mouse model
substantia nigra pars compacta (SNc)
behavioral assay
rotational behavior
estrogen
ovariectomy
Citation
Barry, Mariah J (2020). Rotational Behavior During the Pole Test: A Novel Behavioral Assay in a Mouse Model of Parkinson's Disease. Undergraduate Research Scholars Program. Available electronically from https : / /hdl .handle .net /1969 .1 /188421.