title: Lesion of the medial prefrontal cortex and the subthalamic nucleus selectively affect depression-like behavior in rats.
abstract: Major depression (MD) has been projected to be the first leading cause of disability worldwide. Still, the pathophysiological processes and factors leading to depression remain largely unknown. The present study investigated the differential effects of selective medial prefrontal cortex (mPFC) and subthalamic nucleus (STN) lesions on depression-like and depression-associated behavior in rats, using the following behavioral paradigms: (i) learned helplessness model testing depressive behavior, (ii) elevated plus-maze testing anxious behavior, (iii) 8-arm radial maze testing cognitive performance and (iv) the open-field testing locomotion. Lesion of both, the mPFC or the STN selectively increased depression-like behavior in rats. These effects were not biased by any effects on depression-associated behavior, such as increased anxiety, cognitive impairment or deficits in locomotion. The behavioral data presented in this study support a specific involvement of the mPFC in the pathophysiology of MD and point towards a potent regulatory function of the STN in processing limbic information towards cortical and subcortical regions in the brain pathophysiologically relevant in the manifestation of MD.
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité Campus Mitte, University Medicine Berlin, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Klein
authors.forename: Christine
authors.initials: C
authors.lastname: Winter
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coquery
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: R
authors.initials: R
authors.lastname: Morgenstern
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.forename: Georg
authors.initials: G
authors.lastname: Juckel
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D003863:Depression / Q000503:physiopathology*; D006380:Helplessness, Learned; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000293:injuries / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000502:physiology; D020531:Subthalamic Nucleus / Q000293:injuries / Q000503:physiopathology*; D013997:Time Factors