Establishment of a radiotelemetric recording technique in mice to investigate gastric slow waves: Modulatory role of putative neurotransmitter systems

Abstract

What is the central question of this study? Gastric slow waves originating from the interstitial cells of Cajal-smooth muscle syncytium are usually studied in culture or in tissue segments, but nobody has described recordings of slow waves from awake, freely moving mice. Can radiotelemetry be used to record slow waves, and do they respond predictably to drug treatment? What is the main finding and its importance? Radiotelemetry can be used to record slow waves from awake, freely moving mice, permitting an examination of drug actions in vivo, which is crucial to drug discovery projects for characterizing the effects of drugs and metabolites on gastrointestinal function. The mouse is the most commonly used species in preclinical research, and isolated tissues are used to study slow waves from the interstitial cells of Cajal-smooth muscle syncytium of the gastrointestinal tract. The aim of this study was to establish a radiotelemetric technique in awake mice to record gastric myoelectric activity from the antrum to gain insight into the effects of endogenous modulatory systems on slow waves. Under general anaesthesia, two biopotential wires from a telemetry transmitter were sutured into the antrum of male ICR (imprinting control region) mice. The animals were allowed 1week to recover from surgery before the i.p. administration of drugs to stimulate or inhibit slow waves. The basal dominant frequency of slow waves was 6.96±0.43c.p.m., and the percentages of power in the bradygastric, normogastric and tachygastric ranges were 6.89±0.98, 37.32±1.72 and 34.38±0.77%, respectively (n=74). Nicotine at 1mgkg-1 increased normogastric power, but at 3mgkg-1 it increased bradygastric power (P<0.05). Metoclopramide at 10mgkg-1 increased normogastric power; sodium nitroprusside at 10mgkg-1 had latent effects on tachygastric power (P<0.05); and l-NAME at 10mgkg-1 had no effect (P>0.05). Nicotine and bethanechol also caused varying degrees of hypothermia (>1°C reductions; P<0.05). In conclusion, radiotelemetry can be used to record slow waves from awake, freely moving mice. In light of our findings, we recommend that studies assessing slow waves should also assess body temperature simultaneously.