Effect of serotonin reuptake inhibitor on syndrome development in obese hyperglycemic mice (Umea ob/ob)

These experiments tested the effect of 10 to 30 mg, citalopram/kg body weig ht on food intake, weight increase, and blood glucose levels in young obese hyperglycemic mice (Umea 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 1 0 weeks, when the weight increase is most rapid. Citalopram reduced the wei ght increase at the age 10 to 19 weeks. Food intake reaches a maximum at ag e 7 to 10 weeks and then decreases. The reduction was more rapid in citalop ram-treated mice. The weight of feces paralleled the food intake. Citalopra m treatment had no effect on serum insulin levels in 18-week-old mice. Bloo d 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 tha t, blood sugar values decreased. The decrease was more pronounced in citalo pram-treated mice (P < .01 compared with controls). Blood glucose levels we re 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 correlat ion between accumulated food intake and blood glucose values in individual animals. At age 3 to 10 weeks, ob/ob mice have a high p-cell proliferation rate, and they have large islets of Langerhans. This was not affected by ci talopram treatment. Our findings show that the serotonergic system plays a role as a regulator of food intake over shorter periods, and this is also t rue in the absence of leptin. Copyright (C) 2001 by W.B. Saunders Company.