Brain serotonin plays a crucial role in the regulation of food intake and body weight homeostasis. Previous data suggest an interaction with corticotropin-releasing hormone (CRH). To further examine the interaction between these neurotransmitters, the selective serotonin reuptake-inhibitor (SSRI) fluvoxamine was given intraperitoneally in fa=fa Zucker rats with and without the CRH-receptor-antagonist a-helical CRH administered intracerebroventriculary (i.c.v.). The saline treated animals gained weight. Fluvoxamine led to a significant weight loss while not affecting food intake. Furthermore, insulin levels in this animal model were reduced following fluvoxamine administration. These effects were antagonized by a-helical CRH and are thus most likely mediated via CRH or CRH-like peptides. International Journal of Obesity (2001) IntroductionSelective serotonin reuptake inhibitors (SSRI) are commonly used as drug treatment in depressive disorders. These drugs are well known to centrally affect food intake and body weight homeostasis. This is in accordance with experimental data, demonstrating strong anorectic properties of serotonin when injected into the paraventricular nucleus (PVN) and other hypothalamic areas. 1,2 In the present study we focussed on anorectic properties of the ssri fluvoxamine, which is more specific for serotonin when compared to other compounds of this group of drugs, eg fluoxetine, exerting less effects on the reuptake of noradrenaline. 3 Previous data suggest that, within the PVN, serotonin and corticotropin releasing hormone (CRH) interact to alter food intake and enhanced CRH synthesis has been shown in this particular nucleus following serotonin injection. 4,5 In addition, a stimulating effect of D-fenfluramine, a serotoninreleasing agent, on neuronal activation of CRH expressing cells in the PVN has been demonstrated. 6 CRH clearly possesses anorectic properties, when injected centrally. 7 A causal relationship between the neurotransmitter serotonin and the neuropeptide CRH has, as yet, not been demonstrated. In addition to its anorectic actions, CRH stimulates brown adipose tissue metabolism via activation of the sympathetic nervous system in rodents, when applied centrally, 8,9 potentially causing an increase in energy expenditure.In fa=fa Zucker-rats, CRH 2 -receptor mRNA is reduced in the ventromedial hypothalamus (VMH), suggesting a possible involvement of CRH-neurons in the reduced energy expenditure in this genotype; 10 in addition the hyperinsulinemia in these animals, which is ascribed to an increased activity of vagal efferents to the pancreas, 11 is reduced after local application of CRH to the VMH.This study was aimed at further investigating the nature of brain serotonin and CRH interaction in the control of body weight, which has not been studied before in a long-term in vivo experiment. MethodsChloral hydrate and a-helical CRH were purchased from

Growth hormone (GH) possesses multiple metabolic effects, in particular with regard to glucose and lipid homeostasis. Studies on the effects of GH on body weight and food and water intake are scarce and have yielded controversial results. We investigated the effects of different modes of GH administration on the parameters of body weight and food intake as well as on insulin and leptin concentrations in fa/fa Zucker rats. In control experiments, aqua pro injectione was given. GH was administered over a time period of 11 days at a daily dose of 250 µg intraperitoneally (i.p.) and 25 µg intracerebroventricularly (i.c.v.). While both food intake and body weight were found to be unaltered in the four groups after this observation period, there was an enhanced food intake and consecutively an increase in body weight over the day period when compared to the night period in the groups of rats that received GH i.c.v. or i.p. This tendency was also shown for water intake. Insulin and leptin concentrations were similar in all groups. Thus, injection of GH appears to modify food intake-related behavior, since the periods of enhanced food and water intake were shifted from night- to daytime. Thus, while in general the metabolic parameters remained unchanged, the activity pattern was clearly modified.