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WIREs Membr Transp Signal

Serotonin signaling in eating disorders

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Valérie Compan, Laetitia Laurent, Alexandra Jean, Céline Macary, Joël Bockaert, Aline Dumuis

Published Online: May 09 2012

DOI: 10.1002/wmts.45

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The brain serotonin (5‐hydroxytryptamine, 5‐HT) system is implicated in the neurobiological control of feeding and appears to be dysfunctional in patients suffering from feeding disorders, such as anorexia, bulimia, and obesity. Thanks to the identification and cloning of 5‐HT receptors, the production of agonist and antagonist compounds, and the generation of 5‐HT receptor knock‐out mice, our knowledge on the implication of different 5‐HT receptor subtypes in feeding behavior has greatly increased. A number of studies have demonstrated an involvement of the hypothalamic 5‐HT_1B and 5‐HT_2C receptors in food intake and body weight control, but the downstream events induced by such signaling remain to be explored. Moreover, little is known about the influence of 5‐HT on the rewarding value of eating. Such value may not necessarily be linked to food consumption, but rather to voluntary reduction of food intake, as recently demonstrated upon activation of the 5‐HT₄ receptors in the nucleus accumbens. Thus, abnormalities in the reward system in addition to those in the central control of the autonomic nervous system might contribute to the anorexic behavior. Recent studies have also reported an involvement of the 5‐HT₆ and 5‐HT₇ receptors in feeding behavior. Potential 5‐HT receptor agonists/antagonists could then be developed and used in association with psychological treatment to better cope with the stressors that trigger anorexia and drug dependence. WIREs Membr Transp Signal 2012, 1:715–729. doi: 10.1002/wmts.45

Figure 1.

Schematic representation of (a) brain regions involved in feeding behavior and their innervation by 5‐HT neurons, (b) 5‐HT receptor subtypes present in these brain regions (see also Table 3), and (c) changes in food intake and body weight observed in the different 5‐HTR KO mice (see also Table 2).

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Figure 2.

Adaptive changes in 5‐HT parameters in 5‐HTR KO mice. CX, cortex; GP, globus pallidus; LC, locus coeruleus; OB, olfactory bulb; SN, substantia nigra.

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Figure 3.

Schematic representation of the main 5‐HTR₄ (Gs‐dependent or not) signaling pathways that have been identified in neurons (black) or other cell lines (gray) and in vivo in the nucleus accumbens of mice (red). Among these signaling pathways, anorexia‐like behavior is associated with activation of the cAMP/PKA cascade.

[ Normal View 74K | Magnified View 116K ]

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