TABLE 2.
Overview of brain regions involved in the serotonergic modulation of feeding behavior
| Brain region | Function in the regulation of food intake | Effect of local serotonergic signaling (mechanism) |
|---|---|---|
| Hypothalamus | ||
| ARC | Integration of circulating nutritional and hormonal signals; origin of POMC and AgRP/NPY neurons | Anorexigenic (stimulation of POMC neurons; inhibition of AgRP/NPY neurons) |
| PVN | Major downstream target of POMC and AgRP neurons | Anorexigenic (projections to brainstem regions; synthesis of neuropeptides that modulate food intake) |
| VMN | Downstream target of POMC and AgRP neurons | Anorexigenic (activation of BDNF‐expressing neurons) |
| DMN | Downstream target of POMC and AgRP neurons | Anorexigenic (unknown) |
| LHA | Drives food consumption during hunger; integration with reward centers | Anorexigenic (inhibition of orexin and MCH neurons) |
| Brainstem | ||
| Raphe nuclei | Origin of serotonergic projections toward a variety of brain regions involved in the regulation of feeding behavior | Orexigenic (by inhibition of serotonergic projections via auto‐inhibition) |
| NTS | Integration of peripheral visceral afferents and hormonal signals related to energy status (normally anorexigenic) | Anorexigenic (excitation of POMC neurons and stimulation of glutamatergic projections toward the PBN) |
| PBN | Responds to satiation and noxious signals and controls meal termination; origin of CGRP neurons | Anorexigenic (partly unknown; indirect excitation of CGRP neurons) |
| Thalamus | ||
| PVT | Relay or integration of homeostatic and hedonic control | Unknown |
| Mesolimbic circuitry | ||
| VTA | Origin of dopaminergic projections to mesolimbic circuitry | Anorexigenic (suppression of the motivation for food intake) |
| NAc | Receives most VTA dopaminergic projections; response to food‐predictive cues; incentive motivation for food | Anorexigenic (suppression of the motivation for food intake) Orexigenic through 5‐HT3 and 5‐HT6 receptors |
| CeA | Reward value prediction by integration of homeostatic, cognitive, and visceral inputs | Unknown (serotonin may increase feeding behavior via 5‐HT2A‐expressing CeA neurons) |
Abbreviations: 5‐HT, 5‐hydroxytryptamine; AgRP, agouti‐related protein; ARC, arcuate nucleus; BDNF, brain‐derived neurotrophic factor; CCK, cholecystokinin; CeA, central nucleus of the amygdala; CGRP, calcitonin gene‐related peptide; DMN, dorsomedial nucleus; GLP1, glucagon‐like peptide 1; LHA, lateral hypothalamic area; MCH, melanin‐concentrating hormone; NAc, nucleus accumbens; NPY, neuropeptide Y; NTS, nucleus tractus solitarius; PBN, parabrachial nucleus; PFC, prefrontal cortex; POMC, proopiomelanocortin; PVN, paraventricular nucleus; PVT, paraventricular thalamic nucleus; VMN, ventral medial nucleus; VTA, ventral tegmental area.