In:
Neurogastroenterology & Motility, Wiley, Vol. 27, No. 12 ( 2015-12), p. 1783-1795
Abstract:
Constipation is extremely common in patients with Parkinson's disease ( PD ) and has been described in PD animal models. In this study, we investigated whether a PD ‐like degeneration of dopaminergic neurons of the substantia nigra can influence peristalsis in colonic segments of rats by impacting on enteric dopaminergic transmission. Methods Male, Sprague–Dawley rats received a unilateral injection of neurotoxin 6‐hydroxydopamine (6‐ OHDA ), or saline, into the medial‐forebrain‐bundle. Peristaltic activity was recorded in isolated colonic segments, in baseline conditions and following exposure to combinations of D2 receptor ( DRD 2) agonist sumanirole and antagonist L‐741626. Dopamine levels and DRD 2 expression were assessed in the ileum and colon of animals. We also investigated the involvement of the dorsal motor nucleus of the vagus ( DMV ) — a potential relay station between central dopaminergic denervation and gastrointestinal ( GI ) dysfunction — by analyzing cytochrome c oxidase activity and FosB/DeltaFosB expression in DMV neurons. Key Results We observed profound alterations in the response of colonic segments of 6‐ OHDA lesioned animals to DRD 2 stimulation. In fact, the inhibition of colonic peristalsis elicited by sumanirole in control rats was absent in 6‐ OHDA ‐lesioned animals. These animals also showed reduced DRD 2 expression in the colon, along with elevation of dopamine levels. No significant changes were detected within the DMV . Conclusions & Inferences Our results demonstrate that selective lesion of the nigrostriatal dopaminergic pathway subverts the physiological response of the colon to dopaminergic stimulation, opening new perspectives in the comprehension and treatment of GI dysfunctions associated with PD .
Type of Medium:
Online Resource
ISSN:
1350-1925
,
1365-2982
DOI:
10.1111/nmo.2015.27.issue-12
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2008278-2
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