The effect of depressive-like behavior and antidepressant therapy on social behavior and hierarchy in rats

Boyko, Matthew; Kutz, Ruslan; Grinshpun, Julia; Zvenigorodsky, Vladislav; Gruenbaum, Benjamin F.; Gruenbaum, Shaun E.; Frenkel, Amit; Brotfain, Evgeni; Melamed, Israel; Frank, Dmitry; Zeldetz, Vladimir; Zlotnik, Alexander

doi:10.1016/j.bbr.2019.111953

Cited by 9 publications

(7 citation statements)

References 51 publications

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“…Each rat was placed in the center of the plus maze facing one of the open arms, and the rat’s behavior was videotaped for 5 min for future analysis. The number of entries into the various arms and time spent in arms of the elevated plus maze was recorded with a video camera (Logitech_HD_Pro_Webcam_C920) and subsequently analyzed using Ethovision XT software (Noldus, Wageningen, Netherlands) [ 64 ].…”

Section: Methodsmentioning

confidence: 99%

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety

et al. 2022

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Traumatic brain injury (TBI) affects millions of people worldwide, many of whom are affected with post-TBI mood disorders or behavioral changes, including aggression or social withdrawal. Diminished functionality can persist for decades after TBI and delay rehabilitation and resumption of employment. It has been established that there is a relationship between these mental disorders and brain injury. However, the etiology and causal relationships behind these conditions are poorly understood. Rodent models provide a helpful tool for researching mood disorders and social impairment due to their natural tendencies to form social hierarchies. Here, we present a rat model of mental complications after TBI using a suite of behavioral tests to examine the causal relationships between changes in social behavior, including aggressive, hierarchical, depressive, and anxious behavior. For this purpose, we used multivariate analysis to identify causal relationships between the above post-TBI psychiatric sequelae. We performed statistical analysis using principal component analysis, discriminant analysis, and correlation analysis, and built a model to predict dominant-submissive behavior based on the behavioral tests. This model displayed a predictive accuracy of 93.3% for determining dominant-submissive behavior in experimental groups. Machine learning algorithms determined that in rats, aggression is not a principal prognostic factor for dominant-submissive behavior. Alternatively, dominant-submissive behavior is determined solely by the rats’ depressive-anxious state and exploratory activity. We expect the causal approach used in this study will guide future studies into mood conditions and behavioral changes following TBI.

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Section: Methodsmentioning

confidence: 99%

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety

et al. 2022

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“…The rats were housed in individual cages with free access to two bottles, one with 100 ml of sucrose solution (1% w/v) and the other with 100 ml of water, for 4 h. After this period, the volume (ml) of the consumed sucrose solution and water was recorded. Sucrose preference was calculated as sucrose preference (%) = sucrose consumption (ml)/[sucrose consumption (ml)+water consumption (ml)] × 100% (Boyko et al, 2013b(Boyko et al, , 2019b.…”

Section: Sucrose Preference Testmentioning

confidence: 99%

Blood Glutamate Scavenging With Pyruvate as a Novel Preventative and Therapeutic Approach for Depressive-Like Behavior Following Traumatic Brain Injury in a Rat Model

et al. 2022

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Depression is a common and serious complication following traumatic brain injury (TBI). Both depression and TBI have independently been associated with pathologically elevated extracellular brain glutamate levels. In the setting of TBI, blood glutamate scavenging with pyruvate has been widely shown as an effective method to provide neuroprotection by reducing blood glutamate and subsequent brain glutamate levels. Here we evaluate pyruvate as a novel approach in the treatment and prevention of post-TBI depression-like behavior in a rat model. Rats were divided into five groups: (1) sham-operated control with pyruvate, (2) sham-operated control with placebo, (3) post-TBI with placebo, (4) post-TBI given preventative pyruvate, and (5) post-TBI treated with pyruvate. These groups had an equal number of females and males. Rats were assessed for depressive-like behavior, neurological status, and glutamate levels in the blood and brain. Post-TBI neurological deficits with concurrent elevations in glutamate levels were demonstrated, with peak glutamate levels 24 h after TBI. Following TBI, the administration of either prophylactic or therapeutic pyruvate led to reduced glutamate levels, improved neurologic recovery, and improved depressive-like behavior. Glutamate scavenging with pyruvate may be an effective prophylactic and therapeutic option for post-TBI depression by reducing associated elevations in brain glutamate levels.

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“…However, in contrast to the clinical setting, there is no consensus or universal standard regarding the composition and duration of the observable behavioural phenomena to be termed depressive-like in laboratory mice. Rather, any behaviour that is part of the depressive symptom spectrum is called depressive-like in mouse models, mostly independent from the induction scheme, its severity, composition, or duration [7,16,17,55,[59][60][61][62].…”

Section: Depressive-like Behaviour and The Research Domain Criteriamentioning

confidence: 99%

Introducing a depression-like syndrome for translational neuropsychiatry: a plea for taxonomical validity and improved comparability between humans and mice

et al. 2022

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Depressive disorders are the most burdensome psychiatric disorders worldwide. Although huge efforts have been made to advance treatment, outcomes remain unsatisfactory. Many factors contribute to this gridlock including suboptimal animal models. Especially limited study comparability and replicability due to imprecise terminology concerning depressive-like states are major problems. To overcome these issues, new approaches are needed. Here, we introduce a taxonomical concept for modelling depression in laboratory mice, which we call depression-like syndrome (DLS). It hinges on growing evidence suggesting that mice possess advanced socioemotional abilities and can display non-random symptom patterns indicative of an evolutionary conserved disorder-like phenotype. The DLS approach uses a combined heuristic method based on clinical depression criteria and the Research Domain Criteria to provide a biobehavioural reference syndrome for preclinical rodent models of depression. The DLS criteria are based on available, species-specific evidence and are as follows: (I) minimum duration of phenotype, (II) significant sociofunctional impairment, (III) core biological features, (IV) necessary depressive-like symptoms. To assess DLS presence and severity, we have designed an algorithm to ensure statistical and biological relevance of findings. The algorithm uses a minimum combined threshold for statistical significance and effect size (p value ≤ 0.05 plus moderate effect size) for each DLS criterion. Taken together, the DLS is a novel, biologically founded, and species-specific minimum threshold approach. Its long-term objective is to gradually develop into an inter-model validation standard and microframework to improve phenotyping methodology in translational research.

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The effect of depressive-like behavior and antidepressant therapy on social behavior and hierarchy in rats

Cited by 9 publications

References 51 publications

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety

Blood Glutamate Scavenging With Pyruvate as a Novel Preventative and Therapeutic Approach for Depressive-Like Behavior Following Traumatic Brain Injury in a Rat Model

Introducing a depression-like syndrome for translational neuropsychiatry: a plea for taxonomical validity and improved comparability between humans and mice

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