Abstract
Degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc) induces Parkinson’s disease (PD). Since almost all patients with PD show gastrointestinal (GI) dysfunctions, such as gastroparesis, and GI functions are controlled by neurons in the dorsal motor nucleus of the vagus (DMV), we aimed to determine whether manipulations of the SNpc induces a vagally‐mediated modulation of gastric motility.Microinjection of the retrograde tracer CTB in the DMV labelled neurons in the SNpc, indicating a monosynaptic nigro‐vagal complex connection.In an anesthetized rat preparation in which gastric motility was recorded using miniaturized strain gauges sewn on the anterior stomach wall, NMDA was microinjected in the left SNpc (210nL of a 25mM). In control rats, NMDA increased tone and motility in both the corpus and in the antrum (tone: +211±37, N=11 and +295±53 mg, N= 8; motility: +85±21, N=9 and +82±19%, N=9, of baseline, respectively). This effect was blocked by ipsilateral vagotomy (N=4) or by application to the fourth ventricle of DA‐1 (SCH‐23,390, 45nM) and DA‐2 (L‐741,626, 45nM) antagonists (N=4). In contrast, following microinjection of 6OH‐DA in the SNpc, application of NMDA had no effect on gastric motility (N=4).Our data indicate a monosynaptic connection exists between the SNpc and DMV that modulates gastric tone and motility, suggesting a novel pathway in the regulation of GI functions which may be compromised in PD.Grant Funding Source: DK55530
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