ArticlePharmacology research & perspectives2022
Hypothesis: Amelioration of obesity-induced cognitive dysfunction via a lorcaserin-betahistine combination treatment.
Article in Pharmacology research & perspectives, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- Combination Lorcaserin and Betahistine Treatment Improves Cognitive Dysfunction and Dopaminergic Neuron Activity in a Rat Model of Diet-Induced Obesity.Brain sciences · 2025Article
- Betahistine's Neuroprotective Actions against Lipopolysaccharide-Induced Neurotoxicity: Insights from Experimental and Computational Studies.Brain sciences · 2024Article
- Effects of different dietary energy levels on growth performance, meat quality and nutritional composition, rumen fermentation parameters, and rumen microbiota of fattening Angus steers.Frontiers in microbiology · 2024Article
- Review of Plant Extracts and Active Components: Mechanisms of Action for the Treatment of Obesity-Induced Cognitive Impairment.Brain sciences · 2023Review
- Pharmacological Treatments and Natural Biocompounds in Weight Management.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Hypothesis: Amelioration of obesity-induced cognitive dysfunction via a lorcaserin-betahistine combination treatment.Pharmacology research & perspectives · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.