The proposed studies will focus on characterizing the direct effects of CCK and opioids on neurons in the caudal brainstem which respond to gastric vagal afferent input from the proximal stomach. Selective agonists and antagonists will be directly applied by micropressure on neurons in nucleus tractus solitarius (NTS) and area postrema in the caudal brainstem which respond to proximal gastric vagal input.
The specific aims of the study are to evaluate: 1. The direct effects of CCK and opioids on neurons in the caudal brainstem which respond to gastric vagal input, gastric vagally-evoked (GVE) response. 2. The response of GVE brainstem neurons to CCK and opioids during activation of mechanoreceptors in the antrum and duodenum. 3. The response of GVE brainstem neurons to CCK and opioids during microstimulation of regions of the hypothalamus concerned with the ingestive process. Our previous studies electrophysiologically demonstrated substantial gastric vagal input in the caudal brainstem. We are focusing on the direct central effects of CCK and opioids on gastric sensory neuronal mechanisms. The proposed studies will be conducted on anesthetized cats. Gastric vagal branches from the proximal stomach will electrically stimulated while recording from neurons in nucleus tractus solitarius (NTS) and area postrema in the caudal brainstem. Multibarrel micropipettes will be used to record the GVE response and apply specific agonists and antagonists of CCK and opioids directly on the recording site. A balloon introduced in the antrum and duodenum will be distended to activate mechanoreceptors in the gut wall. The effect of the mechanical distention of the antrum or duodenum on the GVE brainstem response to CCK and opioids will evaluate convergence of input on single neurons. Previous studies demonstrated that neuronal populations in the hypothalamus responded to gastric vagal input. Microstimulation will be used to determine the effect of hypothalamic input on the response of GVE brainstem neurons to CCK and opioids. We feel the proposed studies will provide important information concerning the processing and neuropeptide regulation of gastric vagal input in the brainstem.
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