Chronic social defeat stress model: behavioral features, antidepressant action, and interaction with biological risk factors.
BACKGROUND
Chronic social defeat stress (CSDS) has been proposed as a model of depression. However, most CSDS studies rely only on the analysis of stress-induced social avoidance. Moreover, the predictive validity of the model has been poorly analyzed, let alone its interaction with biological risk factors.


OBJECTIVE
Here, we explore the validity of CSDS as a depression model. Further, the effect of decreased vesicular glutamate transporter 1 (VGLUT1), as a potential factor enhancing a depressive-like phenotype, was studied.


METHODS
Mice were exposed to CSDS (10 days) followed by saline, venlafaxine, fluoxetine, or tianeptine treatment (30 days). The battery of behaviors included motor activity, memory, anxiety, social interaction, helplessness, and anhedonic-like behavior. Moreover, the behavioral effect of CSDS in VGLUT1 heterozygous (VGLUT1+/-) mice was studied, as well as the regulation of VGLUT1 mRNA.


RESULTS
CSDS induced anhedonia, helplessness, hyperactivity, anxiety, social avoidance, and freezing, as well as downregulation of VGLUT1 mRNA in the amygdala. Repeated venlafaxine showed antidepressant-like activity and both venlafaxine and tianeptine behaved as effective anxiolytics. CSDS-induced social avoidance was reverted by tianeptine. Fluoxetine failed to revert most of the behavioral alterations. VGLUT1+/- mice showed an enhanced vulnerability to stress-induced social avoidance.


CONCLUSIONS
We suggest that CSDS is not a pure model of depression. Indeed, it addresses relevant aspects of anxiety-related disorders. Firstly, CSDS-induced anhedonia and social avoidance are not associated in this model. Moreover, CSDS might be affecting brain areas mainly involved in the processing of social behavior, such as the amygdala, where the glutamatergic mechanism could play a key role.
Department of Pharmacology, University of Navarra, 31080 Pamplona, Spain.
E
E
Venzala
A L
AL
García-García
N
N
Elizalde
P
P
Delagrange
R M
RM
Tordera
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics; D001522:Behavior, Animal; D003511:Cyclohexanols / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy / Q000235:genetics; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D012307:Risk Factors; D012919:Social Behavior; D013315:Stress, Psychological / Q000188:drug therapy* / Q000235:genetics*; D013841:Thiazepines / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride; D050598:Vesicular Glutamate Transport Protein 1
D000928:Antidepressive Agents; D003511:Cyclohexanols; D012333:RNA, Messenger; D013841:Thiazepines; D050598:Vesicular Glutamate Transport Protein 1; D005473:Fluoxetine; C050504:tianeptine; D000069470:Venlafaxine Hydrochloride