PT  - JOURNAL ARTICLE
AU  - Manuel Ferreira, Jr
AU  - Niaz Sahibzada
AU  - Min Shi
AU  - William Panico
AU  - Mark Niedringhaus
AU  - Adam Wasserman
AU  - Kenneth J. Kellar
AU  - Joseph Verbalis
AU  - Richard A. Gillis
TI  - CNS Site of Action and Brainstem Circuitry Responsible for the Intravenous Effects of Nicotine on Gastric Tone
AID  - 10.1523/JNEUROSCI.22-07-02764.2002
DP  - 2002 Apr 01
TA  - The Journal of Neuroscience
PG  - 2764--2779
VI  - 22
IP  - 7
4099  - http://www.jneurosci.org/content/22/7/2764.short
4100  - http://www.jneurosci.org/content/22/7/2764.full
SO  - J. Neurosci.2002 Apr 01; 22
AB  - 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 α4β2, 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 α2 adrenergic receptor-mediated inhibition of DMV neurons projecting to the fundus and controlling gastric tone.