Neuroscience Letters 376 (2005) 71–75 Hypothalamic 5-HT 1B -receptor changes in anorectic tumor bearing rats Irina G Makarenko a , Michael M Meguid a,∗ , Louis Gatto b , Carolina G Goncalves a , Eduardo JB Ramos a , Chung Chen c , Michael V Ugrumov d a Department of Surgery, Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, SUNY Upstate Medical University, University Hospital, 750 East Adams Street, Syracuse, NY 13210, USA b Department of Biological Sciences, SUNY at Cortland, Cortland, NY 13045, USA c Department of Statistics, Management Information and Decision, Whitman School of Management, Syracuse University, Syracuse, NY 13244, USA d Laboratory of Hormonal Regulations, Institute of Developmental Biology, Russian, Academy of Sciences, Moscow 117808, Russia Received 21 September 2004; received in revised form 10 November 2004; accepted 11 November 2004 Abstract Serotonin (5-HT) is an anorectic monoamine and its regulatory effects on feeding are mediated primarily via 5-HT 1B -receptors localized in the hypothalamic nuclei, which, apart from the brain stem, are among the most crucial areas of food intake regulation. The distribution of 5-HT 1B -receptors in the hypothalamic nuclei was studied in tumor-bearing (TB) rats at the onset of anorexia and in sham-operated control rats, using the peroxidase-anti-peroxidase immunocytochemical method and specific polyclonal antiserum. Semiquantitative image analysis of 5-HT 1B -receptor immunostaining was performed on high-resolution digital photomicrographs using the NIH Scion Image analysis program and the data were compared using Student’s t-test. Immunostaining detected 5-HT 1B -receptor proteins in the same hypothalamic structures in the Controls as in the TB rats. Qualitative and semiquantitative analysis revealed a significant increase in 5-HT 1B -receptor expression in the magnocellular neurons of paraventricular and supraoptic hypothalamic nuclei in TB rats versus Controls. In contrast, changes were not significant in the parvocellular portion of paraventricular nucleus or in the lateral hypothalamus including perifornical region. These findings emphasize serotonin’s influence on the magnocellular hypothalamic nuclei during developing of cancer anorexia, which is associated with a decrease in food intake. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Anorexia; 5-Hydroxytriptamine; Immunocytochemistry; Paraventricular and supraoptic hypothalamic nuclei; Food intake regulation Decreased food intake and loss of body weight are common features in cancer patients, frequently occurring even before a diagnosis is made, and which ultimately manifest as cancer anorexia–cachexia syndrome. This process has a multifacto- rial origin and its etiology is gradually being defined. Cy- tokines, neuropeptides, neurotransmitters and tumor-derived factors have been implicated as etiologic factors. Serotonin (5-HT) is involved in the regulation of food intake and body weight [3,6]. It is one of the food intake mediators implicated in the development of cancer anorexia–cachexia syndrome [17,27]. ∗ Corresponding author. Tel.: +1 315 464 6277; fax: +1 315 464 6237. E-mail address: meguidm@upstate.edu (M.M. Meguid). The suppressive effect of serotonin and its agonists on ap- petite, and thus on food intake, occurs after both peripheral and central injections. This anorectic effect is mediated via different types of hypothalamic receptors, including those belonging to the 5-HT 1 group [9,12,13], specifically the 5-HT 1B -receptors, which have been investigated in several studies [3,16,29]. We previously described the immunocytochemical dis- tribution of 5-HT 1B -receptors in the hypothalamus of nor- mal Fischer rats [16]. In tumor bearing rats, a decrease in food intake occurs at the onset of cancer anorexia [18,19]. The aim of this study is to characterize the distribution of neurons expressing 5-HT 1B -receptors in the hypothalamic nuclei of anorectic tumor-bearing Fischer rats, compared to controls, and to determine the sites in the hypothala- 0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.11.026