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Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment

The prolonged exposure to obesogenic diets disrupts the mesocortical dopaminergic input to the prefrontal cortex (PFC). This leads to suboptimal dopamine levels in this brain region, which affects cognition and control of food intake. Treatments that restore mesocortical dopaminergic neurotransmissi...

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Autores principales: dela Peña, Ike C., Figueroa, Johnny D., Shi, Wei‐Xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124816/
https://www.ncbi.nlm.nih.gov/pubmed/35599337
http://dx.doi.org/10.1002/prp2.947
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author dela Peña, Ike C.
Figueroa, Johnny D.
Shi, Wei‐Xing
author_facet dela Peña, Ike C.
Figueroa, Johnny D.
Shi, Wei‐Xing
author_sort dela Peña, Ike C.
collection PubMed
description The prolonged exposure to obesogenic diets disrupts the mesocortical dopaminergic input to the prefrontal cortex (PFC). This leads to suboptimal dopamine levels in this brain region, which affects cognition and control of food intake. Treatments that restore mesocortical dopaminergic neurotransmission may improve obesity‐associated cognitive dysfunction and modulate food intake to induce weight loss. Given the complexity and multifactorial nature of obesity, combination treatments would likely achieve sizeable and sustained body weight loss and improve obesity‐linked outcomes, such as cognitive dysfunction. Given this background, we hypothesize that concomitant activation of serotonin 5‐HT2C and histamine H1 receptors, coupled with antagonism of histamine H3 receptors, synergistically modulates mesocortical dopamine neurotransmission and ameliorates obesity‐induced cognitive dysfunction. We propose to test the hypothesis in a diet‐induced obesity (DIO) rat model by treating animals with the 5‐HT2C agonist lorcaserin and the H1 agonist and H3 antagonist betahistine. Consistent with our hypothesis, both lorcaserin and betahistine have been shown to reduce body weight in humans with obesity and animals. Both drugs have been demonstrated to improve cognitive functions by influencing dopaminergic signaling in the PFC. The proposed combination treatment addresses the paucity of studies on obesity treatments that improve cognitive function. This research may also help identify a potential targetable mechanism connecting obesity and neurocognitive outcomes.
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spelling pubmed-91248162022-05-25 Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment dela Peña, Ike C. Figueroa, Johnny D. Shi, Wei‐Xing Pharmacol Res Perspect Original Articles The prolonged exposure to obesogenic diets disrupts the mesocortical dopaminergic input to the prefrontal cortex (PFC). This leads to suboptimal dopamine levels in this brain region, which affects cognition and control of food intake. Treatments that restore mesocortical dopaminergic neurotransmission may improve obesity‐associated cognitive dysfunction and modulate food intake to induce weight loss. Given the complexity and multifactorial nature of obesity, combination treatments would likely achieve sizeable and sustained body weight loss and improve obesity‐linked outcomes, such as cognitive dysfunction. Given this background, we hypothesize that concomitant activation of serotonin 5‐HT2C and histamine H1 receptors, coupled with antagonism of histamine H3 receptors, synergistically modulates mesocortical dopamine neurotransmission and ameliorates obesity‐induced cognitive dysfunction. We propose to test the hypothesis in a diet‐induced obesity (DIO) rat model by treating animals with the 5‐HT2C agonist lorcaserin and the H1 agonist and H3 antagonist betahistine. Consistent with our hypothesis, both lorcaserin and betahistine have been shown to reduce body weight in humans with obesity and animals. Both drugs have been demonstrated to improve cognitive functions by influencing dopaminergic signaling in the PFC. The proposed combination treatment addresses the paucity of studies on obesity treatments that improve cognitive function. This research may also help identify a potential targetable mechanism connecting obesity and neurocognitive outcomes. John Wiley and Sons Inc. 2022-05-22 /pmc/articles/PMC9124816/ /pubmed/35599337 http://dx.doi.org/10.1002/prp2.947 Text en © 2022 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
dela Peña, Ike C.
Figueroa, Johnny D.
Shi, Wei‐Xing
Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment
title Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment
title_full Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment
title_fullStr Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment
title_full_unstemmed Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment
title_short Hypothesis: Amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment
title_sort hypothesis: amelioration of obesity‐induced cognitive dysfunction via a lorcaserin–betahistine combination treatment
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124816/
https://www.ncbi.nlm.nih.gov/pubmed/35599337
http://dx.doi.org/10.1002/prp2.947
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