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We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a &gt;90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [<jats:sup>13<\/jats:sup>C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of \u03b11- and \u03b12- or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-\u03b2-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis. <\/jats:p>","DOI":"10.1152\/ajpgi.00258.2014","type":"journal-article","created":{"date-parts":[[2014,10,3]],"date-time":"2014-10-03T02:22:02Z","timestamp":1412302922000},"page":"G1013-G1023","source":"Crossref","is-referenced-by-count":48,"title":["Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis"],"prefix":"10.1152","volume":"307","author":[{"given":"Luca","family":"Toti","sequence":"first","affiliation":[{"name":"Department of Neural and Behavioral Sciences, Penn State, College of Medicine, Hershey, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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