The Vagal Response To Dopamine Is Altered In A Model Of Parkinsonism
Authors: Bove Cecilia , Anselmi Laura , Travagli R. Alberto 
Published: June 2021

The majority of Parkinson's disease patients experience gastrointestinal dysfunctions such as reduced gastric motility, dysphagia, and severe constipation. Recently, we described the anatomical and pathophysiological characteristics of a nigro‐vagal pathway (PMID28912019), which uses dopaminergic inputs to neurons of the dorsal motor nucleus of the vagus (DMV) to modulate gastric motility. We have also shown that dopamine (DA) modulates the membrane properties of DMV neurons via D1 and D2 receptors (PMID17170022), and that DA administration to the DMV of naïve rats induces mainly a gastroinhibitory response mediated via DA2 receptors (PMID28729246). We have also shown that the gastric response to stimulation of the substantia nigra compacta is impaired in an experimental model of parkinsonism (PMID28912019).In the present study we used a rodent model of parkinsonism with the aim to investigate: 1) the changes in the membrane properties and the responsiveness of DMV neurons, and 2) the gastric tone and motility response to DA microinjections in the DMV.Sprague Dawley rats of both sexes received 3 weekly injections of paraquat (10 mg/kg, i.p.; 10P) or saline (control). Two days after the last paraquat injection, rats showed impaired motor behavior; a group of rats (N=18) was used for whole‐cell patch clamp recordings from DMV neurons, another group (N=6) was used for in vivo testing of gastric tone and motility.Neurons from the 10P group showed reduced input resistance (342±27 vs 573±50 MΩ; N=17 and 12 in 10P and control neurons, respectively; p<0.05) and afterhyperpolarization amplitude and decay kinetics (18±0.9 vs 21±0.8 mV and 98±12 vs 130±10 ms; N=25 and 21 in 10P and controls, respectively; p<0.05).In 50% of 10P and in 62% of controls, perfusion with DA (3–100 □M) induced a concentration‐dependent variation in DMV neuronal firing rate, 25% of the neurons from both groups were depolarized, and 25% and 37.5% were hyperpolarized; the remaining neurons were unresponsive (p>0.05; N=12 and 8 for 10P and control, respectively). Perfusion with the D1 antagonist SCH23,390 increased the firing rate of 10P, but not control, DMV neurons. This excitation was prevented by yohimbine treatment.In 85% of the 34 control animals tested (p<0.05), DA microinjection in the DMV was gastroinhibitory. In all paraquat‐treated animals (N=6), however, microinjection of DA in the DVC induced a biphasic response with an initial increase in gastric tone and motility followed by a profound gastroinhibition. The initial excitatory response was attenuated by pretreatement with the DA1‐like receptor antagonist SCH23,390.These data indicate that the membrane and synaptic properties of DMV neurons are altered in a rodent model of parkinsonism. Indeed, DMV neurons from 10P rats appear to have altered excitability, thus suggesting a maladaptive neural plasticity in the nigro‐vagal pathway that occurs in response to the paraquat‐induced gastric hypomotility.Support or Funding InformationDK 55530This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.