Selective amotivation deficits following chronic psychosocial stress in mice.
Amotivation is a major symptom of several psychiatric disorders. However, which specific motivations are most affected in various illnesses is not well understood. In major depressive disorder (MDD), anecdotal evidence suggests the motivation to explore may be especially affected, but direct evidence from either patients or animal models is lacking. To investigate the potential for, and nature of, exploratory drive deficits in MDD, we subjected mice to a chronic social defeat (CSD) manipulation that gives rise to a MDD-like behavioural ensemble, and performed a behavioural battery to examine bodyweight homeostasis, ambulation, anxiety, exploratory behaviour motivated by either novelty or fear, and short-term memory. Consistent with previous reports, we found a disruption of bodyweight homeostasis and reduced ambulation following CSD treatment, but we found no evidence for anxiogenic effects or impairments in short-term memory. Surprisingly, we also observed profoundly delayed and diminished exploration of novel, safe space following CSD, while exploration motivated by fear remained intact. These results extend our knowledge of the behavioural phenotypes in mice resulting from CSD by homing in on specific motivational drives. In MDD patients, reduced exploration could compound disease symptomatology by preventing engagement in what could be rewarding exploration experiences, and targeting deficits in the motivation to explore may represent a novel avenue for treatment.
Preclinical Laboratory for Translational Research into Affective Disorders, DPPP, Psychiatric Hospital, University of Zurich, August-Forel-Strasse 7, CH-8008, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland; Department of Biology, ETH, Zurich, Switzerland.
Alejandro
A
Tsai Cabal
Preclinical Laboratory for Translational Research into Affective Disorders, DPPP, Psychiatric Hospital, University of Zurich, August-Forel-Strasse 7, CH-8008, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland; Institute for Biomedical Engineering, University and ETH Zurich, CH-8093, Zurich, Switzerland.
Horea-Ioan
HI
Ioanas
Preclinical Laboratory for Translational Research into Affective Disorders, DPPP, Psychiatric Hospital, University of Zurich, August-Forel-Strasse 7, CH-8008, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland; Department of Psychiatry, Psychotherapy and Pesychosomatics (DPPP), Psychiatric Hospital, University of Zurich, Lengstrasse 31, CH-8032, Zurich, Switzerland.
Erich
E
Seifritz
Preclinical Laboratory for Translational Research into Affective Disorders, DPPP, Psychiatric Hospital, University of Zurich, August-Forel-Strasse 7, CH-8008, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland; Department of Psychiatry, Psychotherapy and Pesychosomatics (DPPP), Psychiatric Hospital, University of Zurich, Lengstrasse 31, CH-8032, Zurich, Switzerland. Electronic address: bechara.saab@uzh.ch.
Bechara J
BJ
Saab
D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001835:Body Weight / Q000502:physiology; D002908:Chronic Disease; D003865:Major Depressive Disorder / Q000209:etiology*; D004195:Disease Models, Animal; D004644:Emotions / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D046353:Immobility Response, Tonic / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D021641:Recognition, Psychology / Q000502:physiology; D012930:Social Dominance; D013315:Stress, Psychological / Q000150:complications*
Curiosity; Exploration; Major depressive disorder (MDD); Mice; New frontier task (NFT); Spatial memory