Dissecting the contribution of 5-HT1A auto- and heteroreceptors in sucrose overconsumption in mice
Abstract
The rise in obesity prevalence has been linked to overconsumption of high-sugar containing food and beverages. Recent evidence suggests that chronic sucrose consumption leads to changes in serotonergic neuroplasticity within the neural circuits involved in feeding control. Although there is a relationship between serotonin signalling in the brain and diet-induced obesity, the specific serotonin (5-HT) receptors or pathways involved remain unknown. The 5-HT1A receptor subtype plays a role in regulating mood, anxiety, and appetite, and has been associated with reversing addiction to substances of abuse. However, the respective role of 5-HT1A auto- vs heteroreceptors in sucrose consumption has not been examined. Mice were given controlled access to either 5%, 10% or 25% w/v sucrose, or water as a control, for 12 weeks using the well-established “drinking in the dark” protocol (n = 6–8 mice per group). Ligands selectively targeting 5-HT1A auto- and/or heteroreceptors (NLX-112, unbiased 5-HT1A receptor agonist; NLX-101, preferential heteroreceptor agonist; F13714, preferential autoreceptor agonist) were administered i.p. acutely after 6 and 12 weeks of sucrose consumption. The specific involvement of 5-HT1A receptors in these effects was verified by blockade with the selective 5-HT1A receptors antagonist WAY-100,635. The specific subpopulation of 5-HT1A receptors involved in sucrose consumption was dependent on the concentration of sucrose solution and the duration of exposure to sucrose (6 weeks vs 12 weeks). Long-term sucrose consumption leads to accentuated 5-HT1A autoreceptor function. Thus, targeting 5-HT1A autoreceptors might represent an effective therapeutic strategy to combat the rise in obesity resulting from the overconsumption of high-sugar diet.
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BibTeX
@article{beecher2026dissecting,
title = {{Dissecting the contribution of 5-HT1A auto- and heteroreceptors in sucrose overconsumption in mice}},
author = {Kate Beecher and Joshua Wang and Fatemeh Chehrehasa and Ronan Depoortere and Mark Varney and Adrian Newman-Tancredi and Selena Bartlett and Arnauld Belmer},
journal = {Biomedicine and Pharmacotherapy},
year = {2026},
month = oct,
doi = {10.1016/j.biopha.2022.112699},
url = {https://hal.science/hal-05795102v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Dissecting the contribution of 5-HT1A auto- and heteroreceptors in sucrose overconsumption in mice
AU - Kate Beecher
AU - Joshua Wang
AU - Fatemeh Chehrehasa
AU - Ronan Depoortere
AU - Mark Varney
AU - Adrian Newman-Tancredi
AU - Selena Bartlett
AU - Arnauld Belmer
PY - 2026
DA - 2026/10/12
JO - Biomedicine and Pharmacotherapy
DO - 10.1016/j.biopha.2022.112699
UR - https://hal.science/hal-05795102v1
AB - The rise in obesity prevalence has been linked to overconsumption of high-sugar containing food and beverages. Recent evidence suggests that chronic sucrose consumption leads to changes in serotonergic neuroplasticity within the neural circuits involved in feeding control. Although there is a relationship between serotonin signalling in the brain and diet-induced obesity, the specific serotonin (5-HT) receptors or pathways involved remain unknown. The 5-HT1A receptor subtype plays a role in regulating mood, anxiety, and appetite, and has been associated with reversing addiction to substances of abuse. However, the respective role of 5-HT1A auto- vs heteroreceptors in sucrose consumption has not been examined. Mice were given controlled access to either 5%, 10% or 25% w/v sucrose, or water as a control, for 12 weeks using the well-established “drinking in the dark” protocol (n = 6–8 mice per group). Ligands selectively targeting 5-HT1A auto- and/or heteroreceptors (NLX-112, unbiased 5-HT1A receptor agonist; NLX-101, preferential heteroreceptor agonist; F13714, preferential autoreceptor agonist) were administered i.p. acutely after 6 and 12 weeks of sucrose consumption. The specific involvement of 5-HT1A receptors in these effects was verified by blockade with the selective 5-HT1A receptors antagonist WAY-100,635. The specific subpopulation of 5-HT1A receptors involved in sucrose consumption was dependent on the concentration of sucrose solution and the duration of exposure to sucrose (6 weeks vs 12 weeks). Long-term sucrose consumption leads to accentuated 5-HT1A autoreceptor function. Thus, targeting 5-HT1A autoreceptors might represent an effective therapeutic strategy to combat the rise in obesity resulting from the overconsumption of high-sugar diet.
SN - 0753-3322
SN - 1950-6007
ER -