Distribution and neurochemical characterization of neurons within the nucleus of the solitary tract responsive to serotonin agonist-induced hypophagia.
Pharmacological compounds enhancing serotonergic tone significantly decrease food intake and are among the most clinically efficacious treatments for obesity. However, the central mechanisms through which serotonergic compounds modulate feeding behavior have not been fully defined. The primary relay center receiving visceral gastrointestinal information in the central nervous system is the nucleus of the solitary tract (NTS) in the caudal brainstem. Here we investigated whether the classic anorectic serotonin receptor agonist m-chloro-phenylpiperazine (mCPP) enhances the activity of metabolically sensitive NTS neurons. Using c-fos immunoreactivity (FOS-IR) as a marker of neuronal activation in rats, we observed that mCPP significantly and dose-dependently activated a discrete population of caudal NTS neurons at the level of the area postrema (AP). In particular, this pattern of FOS-IR induction was consistent with the location of catecholamine-containing neurons. Dual-labeling performed with FOS-IR and the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) revealed that mCPP induced FOS-IR in 83.7% of TH-IR containing neurons in the NTS at the level of the AP. The degree of activation of TH neurons was strongly negatively correlated with food intake. Moreover, this activation was specific to catecholamine neurons, with negligible induction of cocaine- and amphetamine-regulated transcript (CART), cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), or neurotensin neurons. NTS catecholaminergic neurons relay visceral gastrointestinal signals to both the lateral hypothalamus (LHA) and paraventricular nucleus of the hypothalamus (PVH), where these signals are integrated into autonomic and hormonal responses regulating food intake. The data presented here identify a novel mechanism through which a serotonin receptor agonist acting in the caudal brainstem may regulate ingestive behavior.
Lam
Daniel D
DD
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Zhou
Ligang
L
Vegge
Andreas
A
Xiu
Philip Y
PY
Christensen
Britt T
BT
Osundiji
Mayowa A
MA
Yueh
Chen-yu
CY
Evans
Mark L
ML
Heisler
Lora K
LK