The Social Defeat Animal Model of Depression Shows
Neuroscience 218 (2012) 138–153 THE SOCIAL DEFEAT ANIMAL MODEL OF DEPRESSION SHOWS DIMINISHED LEVELS OF OREXIN IN MESOCORTICAL REGIONS OF THE DOPAMINE SYSTEM, AND OF DYNORPHIN AND OREXIN IN THE HYPOTHALAMUS C. NOCJAR, a,b* J. ZHANG, c P. FENG a,c AND INTRODUCTION J. PANKSEPP d A reduced ability to experience pleasure, termed anhedo- a Department of Psychiatry, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA nia, is a hallmark symptom of depression and is expressed in rodent models of the illness. Various studies suggest that b Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA a dynorphin and orexin interactive dysfunction between the hypothalamus and the dopamine reward system might c Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, exist in depression; and perhaps cause anhedonia symp- Cleveland, OH, USA toms. Dynorphin and orexin modulate each other’s function d Department of Veterinary and Comparative Anatomy, (Eriksson et al., 2004; Li and van den Pol, 2006) as well as Pharmacology and Physiology, College of Veterinary brain reward mechanisms; though dynorphin typically Medicine, Washington State University, Pullman, WA, USA inhibits and orexin stimulates neural activity (Shippenberg, 2009; Aston-Jones et al., 2010). Dynorphin is also co-expressed in nearly all orexin neurons, which are exclu- Abstract—Anhedonia is a core symptom of clinical depres- sively located in dorsomedial and lateral regions of the sion. Two brain neuropeptides that have been implicated in anhedonia symptomology in preclinical depression mod- hypothalamus (Chou et al., 2001). Importantly, hedonic els are dynorphin and orexin; which are concentrated along behaviors that are commonly diminished in depressed lateral hypothalamic dopamine reward pathways.
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