ASSESSING NON-MOTOR SYMPTOMS IN PARKINSON’S DISEASE USING A 6-HYDROXYDOPAMINE LESION IN THE SUBSTANTIA NIGRA

Abstract

Motor symptoms within Parkinson’s disease (PD) are some of the most well-researched areas, whereas there remains an extensive gap in the literature researching non-motor symptoms, which include sleep, mood, pain and cognitive impairments to name a few. It is well-known that PD affects the brain by depleting dopamine within the nigrostriatal pathway, specifically targeting the substantia nigra, which plays a vital role in producing and controlling motor movements. However, the substantia nigra, as well as dopamine, also play a role in reward and motivation and yet there is still little research done to assess how the degeneration of dopamine within the substantia nigra could impact these cognitive aspects. Pain has also been a common complaint amongst PD patients, yet there is little knowledge of where this pain is coming from or if it is simply a byproduct of the stiffness in muscles that results from PD. Therefore, this project examines both the potential cognitive deficit in decision-making as well as pain as non-motor symptoms in PD over time. In this study, forty Sprague-Dawley rats were subjected to learn a novel version of the Rat Gambling Task (RGT). Then, they were subjected to the Mechanical Paw Withdrawal Threshold (MPWT) test to establish no prior allodynia. After they successfully learned the RGT, they underwent stereotaxic surgery to inject either 1 µl of saline or 1 µl of 6-hydroxydopamine (6-OHDA) (5µg/µl dissolved in 0.9% saline and 0.02% ascorbic acid). Animals were then either tested at two weeks or four weeks, as prior literature has suggested maximum dopamine depletion at four weeks. Animals were placed in one of four groups: saline 2 weeks, 6-OHDA 2 weeks, saline 4 weeks or 6-OHDA 4 weeks. After two weeks, animals in the first two groups were tested using the RGT to assess cognitive performance in decision-making. To assess pain thresholds, animals were subjected to the MPWT, as well as the open field task. At four weeks, animals in the latter two groups were assessed the same way. Results indicated a significant difference found between animals injected with 6-OHDA tested at 2 weeks in that they scored significantly lower in percent accuracy within the RGT than the other two saline groups. Surprisingly, there was no difference between the animals in the 6-OHDA 4 weeks group and any other group. Animals in the 6-OHDA 2 weeks group also showed higher omissions in the RGT when tested at 2 weeks than they had done at baseline. Regarding pain, there was no difference between any group in either paw when assessing for hypersensitivity. The results of this study indicate a potential link between cognitive impairments (decision-making) and PD, which should lead to more research being done in this field in order to fully understand the underlying mechanisms. As for pain, there is still work to be done to uncover the etiology of the pain that is experienced by PD patients. It is imperative to continue research to uncover a comprehensive understanding of these non-motor symptoms within PD.