title: Risperidone-induced weight gain and reduced locomotor activity in juvenile female rats: The role of histaminergic and NPY pathways.
abstract: Second generation antipsychotic drugs (SGAs) such as risperidone are increasingly prescribed (mostly for off-label use) to children and adolescents for treating various mental disorders. SGAs cause serious weight gain/obesity and other metabolic side-effects. This study aimed to establish an animal model of risperidone-induced weight gain in female juvenile rats, and to investigate the effects of risperidone on the expression of hypothalamic histaminergic H1 receptors (H1R) and neuropeptides, and their association with weight gain. Female Sprague Dawley rats were treated orally with risperidone (0.3mg/kg, 3 times/day) or vehicle (control) starting from postnatal day (PD) 23 (±1 day) for 3 weeks (a period corresponding to the childhood-adolescent period in humans). In the female juvenile rats, risperidone treatment increased food intake and body weight gain, which started to appear after 12 days' treatment. Risperidone also significantly decreased the locomotor activity of the female rats. Consistently, risperidone significantly elevated mRNA expression of hypothalamic H1R, neuropeptide Y (NPY), and agouti-related peptide (AgRP) compared to controls, and H1R and NPY levels were correlated with risperidone enhanced weight gain and food intake in the female juvenile rats. However, risperidone did not affect hypothalamic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA expression. Therefore, these results suggested that risperidone elevated appetite and body weight gain in juveniles via regulation of the hypothalamic H1R, NPY and AgRP pathways, as well as by reducing activity.
authors.affiliation: Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong 2522, NSW, Australia; School of Medicine, University of Wollongong, Wollongong 2522, NSW, Australia.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Lian
authors.affiliation: Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong 2522, NSW, Australia; School of Medicine, University of Wollongong, Wollongong 2522, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: De Santis
authors.affiliation: Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong 2522, NSW, Australia; School of Medicine, University of Wollongong, Wollongong 2522, NSW, Australia.
authors.forename: Meng
authors.initials: M
authors.lastname: He
authors.affiliation: Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong 2522, NSW, Australia; School of Medicine, University of Wollongong, Wollongong 2522, NSW, Australia. Electronic address: chao@uow.edu.au.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009478:Neuropeptide Y / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D054369:Agouti-Related Protein; D014150:Antipsychotic Agents; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D018967:Risperidone
keywords: Histamine receptor; Juvenile rats; Locomotor activity; Neuropeptide Y; Risperidone; Risperidone (PubChem CID: 5073); Weight gain