title: Amitriptyline is efficacious in ameliorating muscle inflammation and depressive symptoms in the mdx mouse model of Duchenne muscular dystrophy.
abstract: Mutations in the structural protein dystrophin underlie muscular dystrophies characterized by progressive deterioration of muscle function. Dystrophin-deficient mdx mice are considered a model for Duchenne muscular dystrophy (DMD). Individuals with DMD are also susceptible to mood disorders, such as depression and anxiety. Therefore, the study objectives were to investigate the effects of the tricyclic antidepressant amitriptyline on mood, learning, central cytokine expression and skeletal muscle inflammation in mdx mice. Amitriptyline-induced effects (10 mg kg(-1) daily s.c. injections, 25 days) on the behaviour of mdx mice were investigated using the open field arena and tail suspension tests. The effects of chronic amitriptyline treatment on inflammatory markers were studied in the muscle and plasma of mdx mice, and mood-associated monoamine and cytokine concentrations were measured in the amygdala, hippocampus, prefrontal cortex, striatum, hypothalamus and midbrain. The mdx mice exhibited increased levels of anxiety and depressive-like behaviour compared with wild-type mice. Amitriptyline treatment had anxiolytic and antidepressant effects in mdx mice associated with elevations in serotonin levels in the amygdala and hippocampus. Inflammation in mdx skeletal muscle tissue was also reduced following amitriptyline treatment as indicated by decreased immune cell infiltration of muscle and lower levels of the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the forelimb flexors. Interleukin-6 mRNA expression was remarkably reduced in the amygdala of mdx mice by chronic amitriptyline treatment. Positive effects of amitriptyline on mood, in addition to its anti-inflammatory effects in skeletal muscle, may make it an attractive therapeutic option for individuals with DMD.
authors: Department of Physiology, University College Cork, Cork, Ireland Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
authors: Jennifer
authors: J
authors: Manning
authors: Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
authors: Rebecca
authors: R
authors: Kulbida
authors: Department of Biomedical Sciences, Creighton University, School of Medicine, Omaha, NE, USA Department of Neurology, Creighton University, School of Medicine, Omaha, NE, USA.
authors: Prerana
authors: P
authors: Rai
authors: Department of Neurology, Creighton University, School of Medicine, Omaha, NE, USA.
authors: Lindsay
authors: L
authors: Jensen
authors: Department of Biomedical Sciences, Creighton University, School of Medicine, Omaha, NE, USA.
authors: Judith
authors: J
authors: Bouma
authors: Department of Neurology, Creighton University, School of Medicine, Omaha, NE, USA.
authors: Sanjay P
authors: SP
authors: Singh
authors: Department of Physiology, University College Cork, Cork, Ireland.
authors: Dervla
authors: D
authors: O'Malley
authors: Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland Department of Biomedical Sciences, Creighton University, School of Medicine, Omaha, NE, USA denizyilmazer-hanke@creighton.edu d.omalley@ucc.ie.
authors: Deniz
authors: D
authors: Yilmazer-Hanke
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D007858:Learning / Q000187:drug effects; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline