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Parkinson’s disease (PD) is a progressive neurodegenerative disorder that can also affect gastrointestinal (GI) function. External factors, such as chronic stress, have been shown to play a role in the development of PD. GI disorders, include constipation that is a common non-motor symptom of PD that affects around 80% of patients. Defecation is under voluntary control, beginning from centres in the brain, sending signals down the spinal cord to the lumbosacral defecation centre. However, the mechanisms involved in PD-associated constipation remain unknown. The toxin affecting catecholamine neurons, 6-hydroxydopamine (6-OHDA), is commonly used to model PD and causes constipation when injected into the medial forebrain bundle (MFB). In Chapter 3, I have shown that 6-OHDA rats developed motor dysfunction as well as deficits in colon motility, exhibited by a significantly increased bead expulsion time compared with shams. Furthermore, the number of contractions and propulsion of contents by 6-OHDA rats was significantly reduced in comparison to shams after the administration of capromorelin, a colokinetic that acts on the lumbosacral spinal cord, indicating that 6-OHDA animals have reduced responsiveness of the defecation circuits. Enteric neuropathy was observed in the distal colon, revealing that 6-OHDA lesioning of the MFB has downstream effects at the cellular level. Based on the results of Chapter 3, it leaves open two questions that are addressed in Chapter 4: is the responsiveness of neurons downstream from the spinal defecation centres affected by 6-OHDA and could leakage of 6-OHDA into the periphery contribute to the changed responsiveness. In order to investigate the first question, I used prucalopride, another colokinetic which acts on 5-HT4 receptors in the ENS, and found that there was a trend for reduced responsiveness to prucalopride in 6-OHDA rats compared with shams. This suggests there may be a deficiency at the level of the ENS. To address the second