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Eating a High Fat Diet Enhances Sensitivity of Rats to Serotonin Syndrome
Author(s) -
Beltran Nina,
Ramos Jeremiah,
Landavazo Antonio,
Blough Bruce,
Serafine Katherine
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03343
Subject(s) - medicine , endocrinology , agonist , serotonin , 5 ht receptor , analysis of variance , receptor , 5 ht1a receptor , 8 oh dpat , obesity , behavioural despair test , antidepressant , hippocampus
Drugs that act on serotonin (5‐HT) systems are important for the treatment of many conditions, including anxiety, depression, and obesity. One potential adverse effect of these drugs is the development of 5‐HT syndrome. Animal models of 5‐HT syndrome include lower lip retraction, flat body posture, and forepaw treading. Diet (e.g., type and amount of food consumed) has been shown to directly impact sensitivity of rats to 5‐HT syndrome. For example, eating high fat chow increases sensitivity of rats to 5‐HT 1A receptor agonist 8‐OH‐DPAT‐induced lower lip retraction; however, it is not known if eating high fat chow also impacts sensitivity of rats to other 5‐HT syndrome behaviors, other 5‐HT receptor agonists (e.g., 5‐HT 2C receptor agonists), or if these effects are different among females as compared to males. To test the hypothesis that eating high fat chow enhances the sensitivity of rats to 5‐HT syndrome, male and female rats eating high fat (60% kcal from fat) or standard (17% kcal from fat) chow were tested once weekly with cumulative doses of 8‐OH‐DPAT (0.01‐1.0 mg/kg, s.c.), and two different 5‐HT 2C receptor agonists (lorcaserin [1.0‐32.0 mg/kg, i.p.], and WAY 163909 [1.0‐32.0 mg/kg, i.p.]). Both lorcaserin and WAY 163909 induced forepaw treading in male and female rats. After 5 weeks, 3‐way partially repeated measures ANOVAs and Bonferroni's post hoc multiple comparisons tests revealed that forepaw treading induced by both drugs was enhanced among rats eating high fat chow. Eating high fat chow enhanced sensitivity of male rats to lorcaserin‐induced forepaw treading to a greater extent than in females. However, eating high fat chow enhanced sensitivity of females to WAY 163909‐induced forepaw treading to a greater extent than in males. 8‐OH‐DPAT‐induced lower lip retraction, flat body posture, and forepaw treading in male and female rats. 8‐OH‐DPAT induced more lower lip retraction among male rats than female rats, and more lower lip retraction among rats eating high fat chow (in both sexes) than rats eating standard chow. Additionally, 8‐OH‐DPAT induced more flat body posture among male rats than female rats. These results suggest that sex and dietary history (e.g., patients diagnosed with obesity) could influence sensitivity to therapeutic and adverse effects of serotonergic drugs.