Background and aims: Gastroparesis is a common non-motor system symptom of Parkinsons disease.However, the mechanism responsible for the gastric motor abnormality is not clear.We previously have reported the impaired gastric motility in the rats with bilateral substantia nigra (SN) subjected to 6-hydroxydopamine (6-OHDA) (6-OHDA rats).In the present study, we explored the neurochemical changes of vagal motoneurons and enteric nervous system (ENS) involved in the gastric dysmotility in the 6-OHDA rats.Methods: The strain gauge force transducer, digital X-ray imaging system, western blot, immunofluorecence and Radio Immunoassay were used in this study.Results: Following 6-OHDA microinjected bilaterally into the SN, the number of tyrosine hydroxylaseimmunoreactive (TH-IR) neurons and dopamine (DA) content in the lesioned SN were greatly reduced.In 6-OHDA rats, the expression of choline acetyltransferase (ChAT) (P<0.01) and the content of acetylcholine (ACh) (P<0.05)were reduced in the dorsal motor nucleus of the vagus (DMV).To ascertain whether the decreased ACh could influence gastric neurotransmitters, we measured expression of TH and ChAT, and content of DA, noradrenaline (NE) and ACh in the gastric muscularis externa.The protein level of TH (P<0.05) was significantly enhanced, but ChAT was reduced (P<0.05) in the 6-OHDA rats, where, correspondingly, DA content (P<0.01) was also markedly increased, while ACh level (P<0.05) was decreased.But, no alteration of NE level was observed in the 6-OHDA rats.We also found α-synuclein immunoreactive inclusion in the gastric myenteric plexus of the 6-OHDA rats.Next, we detected the expressions of dopaminergic D1 and D2 receptors in the 6-OHDA rats.The expression of D2 receptor (P<0.001) was extrcmely increased, while D1 was not changed.Furthermore, we still observed an impaired gastric motility and delayed gastric emptying in the 6-OHDA rats, which is same as our previous report.IV infusion of domperidone (D2 receptor antagonist), but not SCH2390 (D1 receptor antagonist) increased the frequency and amplitude of contractions by 90% in the 6-OHDA rats.To investigate the mechanism responsible for the enhanced production of DA contents and D2 receptors in the stomach, we demonstrated that subdiaphragmatic vagotomy at the time of 6-OHDA treatment prevented the increase in TH and D2 receptor expression in the gastric myenteic plexus and reduction in gastric motility in 6-OHDA rats.Conclusion: Decreased excitatory ACh, and enhanced inhibitory DA and D2 receptor in the gastric muscular layer may contribute to the gastric hypomotility in the 6-OHDA rats.These results suggest that destruction of SN dopaminergic system caused DMV cholinergic neurons dysfunction may affect the ENS and then lead to an impaired gastric motility.