Intranasal 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Administration Hampered Contractile Response of...

Background: Gastrointestinal (GI) disturbances occur frequently in the early premotor stage of Parkinson's disease (PD). These GI impairments are associated, at least in part, with dopaminergic dysfunction in the myenteric plexus. However, the enteric nervous system (ENS) pathophysiology underlying GI dysfunction in PD has been overlooked. Objectives: The aim of this study was to evaluate the premotor GI disturbances in rats submitted to intranasal (i.n.) MPTP, a valid experimental model of the premotor stage of PD. Methods: Ileum segments from male Wistar rats (21 weeks old) were collected 12 days following the i.n. MPTP administration for functional studies. Isometric contractile concentration-response (CR) curves (cumulative) for dopamine (DA) were performed in both the presence and absence of sulpiride, a selective dopamine D2-like receptor (D2R) antagonist. Results: Functional studies showed that DA induced a concentration-dependent contractile response in the ileum, which exhibited marked contraction at lower concentrations (0.01-0.9 µM) and relaxation at higher concentrations (3-90 µM). MPTP significantly attenuated both the contraction and the ensuing relaxation. Furthermore, sulpiride significantly reduced the contractile response to DA in the control group and blocked the relaxation in the MPTP group. The MPTP-induced dysmotility occurred with preserved DA homeostasis, as shown by normal DA, TH, and D2R ileal levels in the MPTP group. However, MPTP seemed to impose a decrease in S100β and GFAP (enteroglial markers) immunostaining in the ileal myenteric plexus. Conclusions: In summary, we provide pioneering functional, neurochemical, and morphological evidence showing that rats submitted to the i.n. MPTP model exhibited premotor DA-dependent ileum motile dysfunction accompanied by enteroglial disturbance within the myenteric plexus, but with preserved DA markers.