title: Behavioral, hormonal and central serotonin modulating effects of injected leptin.
abstract: Leptin is viewed as an important target for developing novel therapeutics for obesity, depression/anxiety and cognitive dysfunctions. The present study therefore concerns behavioral, hormonal and central serotonin modulating effects of systemically injected leptin. Pharmacological doses (100 and 500 μg/kg) of leptin injected systemically decreased 24h cumulative food intake and body weight in freely feeding rats and improved acquisition and retention of memory in Morris water maze test. Potential anxiety reducing, hormonal and serotonin modulating effects of the peptide hormone were determined in a separate experiment. Animals injected with 100 or 500 μg/kg leptin were tested for anxiety in an elevated plus maze test 1h later. A significant increase in the number of entries and time passed in open arm of the elevated plus maze in leptin injected animals suggested pronounced anxiety reducing effect. Moreover, circulating levels of leptin correlated significantly with anxiety reducing effects of the peptide hormone. Serum serotonin increased and ghrelin decreased in leptin injected animals and correlated, positively and negatively respectively, with circulating leptin. Corticosterone increased at low dose and levels were normal at higher dose. Serotonin metabolism in the hypothalamus and hippocampus decreased only at higher dose of leptin. The results support a role of leptin in the treatment of obesity, anxiety and cognitive dysfunctions. It is suggested that hormonal and serotonin modulating effects of leptin can alter treatment efficacy in particularly comorbid conditions.
authors.affiliation: Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi, Pakistan; Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi, Pakistan. Electronic address: djhaleem@uok.edu.pk.
authors.forename: Darakhshan J
authors.initials: DJ
authors.lastname: Haleem
authors.affiliation: Department of Biochemistry, Dow University of Health Sciences, Karachi, Pakistan.
authors.forename: Zeba
authors.initials: Z
authors.lastname: Haque
authors.affiliation: Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Qurrat-ul-Aen
authors.initials: QU
authors.lastname: Inam
authors.affiliation: Neurochemistry and Biochemical Neuropharmacology Research Laboratory, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Huma
authors.initials: H
authors.lastname: Ikram
authors.affiliation: Department of Biomedical Engineering, Sir Syed University of Engineering and Technology, Karachi, Pakistan.
authors.forename: Muhammad Abdul
authors.initials: MA
authors.lastname: Haleem
mesh_terms: D000818:Animals; D001007:Anxiety / Q000097:blood / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D054439:Ghrelin / Q000097:blood; D007031:Hypothalamus / Q000187:drug effects; D007267:Injections; D020738:Leptin / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood*
chemical_list: D054439:Ghrelin; D020738:Leptin; D012701:Serotonin
keywords: Anxiety; Cognition; Depression; Ghrelin; Leptin; Obesity; Serotonin