Alterations of colonic cholinergic and tachykininergic motility in a rat model of Parkinson's Disease

Objective: Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neurons. PD patients can develop gastrointestinal motor dysfunctions and alterations of enteric nervous system. This study examines the patterns of colonic neuromuscular excitatory cholinergic and tachykininergic pathways in rats bearing a neurotoxic lesion of the nigrostriatal pathway reminiscent of PD. Methods: Nigrostriatal degeneration was induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of rats. Animals were sacrificed 28 or 56 days after surgery. Colonic longitudinal muscle preparations were set up in organ baths, and connected to isometric transducers to record contractions (g/g tissue) elicited by electrical stimulation (ES, 10 Hz), in the presence of guanethidine and Nxnitro- L-arginine methylester. L-732,138 (NK1 receptor antagonist) or atropine were used to record contractions driven by acetylcholine or tachykinins, respectively. Contractions elicited by exogenous substance P (SP, 10 μ mol L-1) or carbachol (10 μ mol L-1) were also recorded. Results: In control preparations incubated with L- 732,138, ES evoked cholinergic contractions (49.6 ± 5.3), which were reduced in 6-OHDA lesioned rats at 28 and 56 days (31.3 ± 4.6 and 37.7 ± 2.3, respectively). Carbachol-evoked contractions were enhanced in 6-OHDA lesioned rats both at 28 and 56 days (92.6 ± 3.3 and 91.7 ± 2.4, respectively), as compared with controls (51.7 ± 4.4). In the presence of atropine, electrically evoked tachykininergic contractions were enhanced in 6-OHDA lesioned rats at 56 days, as compared with controls (49.1 ± 4.1 vs 28.7 ± 3.8). Contractions elicited by exogenous SP were enhanced in tissues from 6-OHDA lesioned rats both at 28 (45.0 ± 5.3) and 56 days (77.2 ± 4.2), in comparison with controls (27.0 ± 1.9). Conclusion: Experimental PD, elicited by nigrostriatal dopaminergic degeneration, is associated with changes in neurotransmitter pathways driving the excitatory motor functions of colon: an impairment of cholinergic transmission occurs in concomitance with an enhancement of tachykininergic control. Such a shift takes place along with an up-regulation of contractile responses mediated by muscular muscarinic receptors, which might be compensatory in nature.