title: Leptin resistance elicits depressive-like behaviors in rats.
abstract: There is a growing appreciation that the complications of obesity extend to the central nervous system (CNS) and include increased risk for development of neuropsychiatric co-morbidities such as depressive illness. The neurological consequences of obesity may develop as a continuum and involve a progression of pathological features which is initiated by leptin resistance. Leptin resistance is a hallmark feature of obesity, but it is unknown whether leptin resistance or blockage of leptin action is casually linked to the neurological changes which underlie depressive-like phenotypes. Accordingly, the aim of the current study was to examine whether chronic administration of a pegylated leptin receptor antagonist (Peg-LRA) elicits depressive-like behaviors in adult male rats. Peg-LRA administration resulted in endocrine and metabolic features that are characteristic of an obesity phenotype. Peg-LRA rats also exhibited increased immobility in the forced swim test, depressive-like behaviors that were accompanied by indices of peripheral inflammation. These results demonstrate that leptin resistance elicits an obesity phenotype that is characterized by peripheral immune changes and depressive-like behaviors in rats, supporting the concept that co-morbid obesity and depressive illness develop as a continuum resulting from changes in the peripheral endocrine and metabolic milieu.
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA; Department of Psychology, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Macht
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vazquez
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Petyak
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Grillo
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kaigler
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Enos
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: McClellan
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Cranford
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Murphy
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Nyland
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Solomon
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Gertler
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA; W.J.B. Dorn VA Medical Center, Columbia, SC 29208, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA; W.J.B. Dorn VA Medical Center, Columbia, SC 29208, USA. Electronic address: lawrence.reagan@uscmed.sc.edu.
authors.forename: L P
authors.initials: LP
authors.lastname: Reagan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D003863:Depression / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D020738:Leptin / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D020738:Leptin
keywords: Activated T cells; Adiposity; C-reactive protein; Forced swim test; Inflammation; Obesity; Pegylated leptin receptor antagonist; Spleen; Triglycerides