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The Journal of Neuroscience, April 1, 2002, 22(7):2764-2779

CNS Site of Action and Brainstem Circuitry Responsible for the Intravenous Effects of Nicotine on Gastric Tone

Manuel Ferreira Jr¹, Niaz Sahibzada^{1, 3}, Min Shi², William Panico¹, Mark Niedringhaus¹, Adam Wasserman¹, Kenneth J. Kellar¹, Joseph Verbalis², and Richard A. Gillis¹

¹ Department of Pharmacology and ² Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, and ³ Department of Psychology, University of the District of Columbia, Washington, DC 20008

The purposes of our study were to determine (1) the effects of intravenous (i.v.) nicotine on gastric mechanical function of anesthetized rats, (2) the CNS site of action of nicotine to produce these effects, (3) the CNS nicotinic acetylcholine receptor (nAChR) subtype(s) responsible for mediating the i.v. effects of nicotine, and (4) the brainstem neurocircuitry engaged by i.v. nicotine for eliciting its gastric effects. This was accomplished by monitoring intragastric pressure (gastric tone) and contractility of the fundus and antrum while administering five doses of i.v. nicotine and microinjecting nicotine into specific brainstem nuclei. Additionally, c-Fos expression in the brainstem after i.v. nicotine and pharmacological agents were used as tools to identify the CNS site and circuitry and reveal the nAChR subtype(s) mediating the gastric effects of nicotine. Using these experimental approaches, we found the following. (1) When given intravenously in doses of 56.5, 113, 226, 452, and 904 nmol/kg, nicotine elicited only inhibitory effects on gastric mechanical function. The most sensitive area of the stomach to nicotine was the fundus, and this effect was mediated by the vagus nerve at doses of 56.5, 113, and 226 nmol/kg. (2) The CNS site of action and nAChR subtype responsible were glutamatergic vagal afferent nerve terminals in the medial subnucleus of the tractus solitarious (mNTS) and 42, respectively. (3) The brainstem neurocircuitry that was involved appeared to consist of a mNTS noradrenergic pathway projecting to the dorsal motor nucleus of the vagus (DMV). This pathway seems to be activated via nitriergic interneurons engaged by vagally released glutamate in the mNTS and results in 2 adrenergic receptor-mediated inhibition of DMV neurons projecting to the fundus and controlling gastric tone.

Key words: vagus; mNTS; DMV; c-Fos; nicotinic; gastric tone; gastric motility; intragastric pressure

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Copyright © 2002 Society for Neuroscience  0270-6474/02/2272764-16$05.00/0

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