Effect of serotonin reuptake inhibitor on syndrome development in obese hyperglycemic mice (Umeå ob/ob).
These experiments tested the effect of 10 to 30 mg, citalopram/kg body weight on food intake, weight increase, and blood glucose levels in young obese hyperglycemic mice (Umeå ob/ob). A leptin defect in ob/ob mice results in hyperphagia, hyperglycemia, and increased body weight compared with normal mice. Citalopram had no effect on weight increase in ob/ob mice aged 3 to 10 weeks, when the weight increase is most rapid. Citalopram reduced the weight increase at the age 10 to 19 weeks. Food intake reaches a maximum at age 7 to 10 weeks and then decreases. The reduction was more rapid in citalopram-treated mice. The weight of feces paralleled the food intake. Citalopram treatment had no effect on serum insulin levels in 15-week-old mice. Blood sugar values in fed mice reached a peak at age 7 weeks (21.7 +/- 1.7 mmol/L in controls and 22.3 +/- 1 mmol/L in citalopram-treated mice). After that, blood sugar values decreased. The decrease was more pronounced in citalopram-treated mice (P < .01 compared with controls). Blood glucose levels were lower at ages 12 to 15 weeks in female ob/ob control mice (13.6 +/- 2.5 mmol/L v 19.0 +/- 0.6 mmol/L in male control mice; P < .05). The effect of citalopram was the same in male and female mice. There was a close correlation between accumulated food intake and blood glucose values in individual animals. At age 3 to 10 weeks, ob/ob mice have a high beta-cell proliferation rate, and they have large islets of Langerhans. This was not affected by citalopram treatment. Our findings show that the serotonergic system plays a role as a regulator of food intake over shorter periods, and this is also true in the absence of leptin.
Department of Integrative Medical Biology, Umeå University, Sweden.
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Thrybom
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Rooth
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Lindström
D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005243:Feces; D005260:Female; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors