The long term objective is to determine how the vagal nuclei in the medulla interact with the lateral hypothalamus in the cat to mediate excitation of phasic antral contractions of the stomach in the absence of an effect on gastric acid secretion. Disorders of gastric motor function such as tachygastria and delayed gastric emptying occur often in the absence of alterations in acid secretion. By analogy with cardiac arrhythmias, vagally-mediated influences from the brain might be expected to be involved, yet electrical stimulatioin of efferent vagal trunks regularly excites acid secretion, phasic gastric contractions, and increases in plasma gastrin in parallel. Now that efferent motor vagal pathways for excitation of phasic antral contractions have been demonstrated in both the nucleus ambiguus and the lateral hypothalamus of cats, it is appropriate to explore the hypothesis that a common pathway might be involved, sharing neurotransmitters and neuromodulators, and also participating in vago-vagal reflex control mechanisms. The methodology to be used involves stereotaxic guided introduction of double barrelled cannulae into the NA or DMNV. This permits either electrical stimulation or chemostimulation by microinjection of putative neurotransmitters or neuromodulators. GABA Receptor antagonists will be injected into the NA and substance P or 5-hydroxytryptamine into the DMNV. By constructing dose-response curves, submaximal or subthreshold doses of these agonists can be combined with low doses of electrical stimulation and evidence for neuromodulation obtained. In order to determine the role of vagal afferents which might participate in such a system, the proximal cut end of a cervical or thoracic vagus trunk will be stimulated electrically and the effects of electrolytic lesions or of microinjection of procaine into the NTS on phasic antral contractions will be determined. The effect of microinjection of inhibitory agents into the NA or DMNV on the motor response will allow an interpretation of the role of these nuclei in mediating vago-vagal reflexes. Finally microinjection of muscimol into the NA and electrolytic lesions of the NA and DMNV during electrical lateral hypothalamic stimulation will be made. Dose response studies with muscimol and bicuculline will permit selected doses to be combined with afferent vagal stimulation.
| Lynn, R B; Feng, H S; Han, J et al. (1991) Gastric effects of thyrotropin-releasing hormone microinjected into the dorsal vagal nucleus in cats. Life Sci 48:1247-54 |
