Male and female 5-HT(1B) receptor knockout mice have higher body weights than wildtypes.

5-HT(1B) receptors have a regulatory role in serotonergic activity and influence feeding behavior and body weight. Because the absence of 5-HT(1B) receptors may cause changes in this regulation, body weight was measured in male and female 5-HT(1B) receptor knockout (5-HT(1B) KO) and wildtype (WT) mice from weaning until the age of 30 weeks. In both genders, 5-HT(1B) KO mice had a higher body weight than WT mice (17% and 9%, respectively). Body weight was significantly higher for males over the entire period and for females from Week 18 onwards. Absolute food and water consumption were related to body weight. However, relative to body weight, males consumed more than females. 5-HT(1B) KO males drank strikingly more water. Housing mice singly reduced food and water intake in males, but not in females. Plasma leptin levels and most organ weights did not differ between genotypes, indicating that higher body weight in 5-HT(1B) KO mice is not related to obesity. Relative to body weight, brains and adrenals were larger in females, while heart and liver were smaller. Kidneys were smaller in females, but larger in 5-HT(1B) KO mice, while lungs showed opposite effects. Spleen and testes were smaller in 5-HT(1B) KO mice. Although 5-HT(1B) KO males are more aggressive, testosterone levels were not different from WT mice. Basal corticosterone levels were similar in all groups and increased in response to mild stress, particularly in females. Lifelong absence of 5-HT(1B) receptors in mice resulted in clear phenotypic differences in body weights and food and water intake. Lacking this receptor increases body growth, without signs of obesity. A potential genetic background effect influencing this phenotype is discussed.