Neurobehavioral deficits in db/db diabetic mice

Abstract

Recent clinical studies indicate neurobehavioral disturbances in type-2 diabetics. However, there is paucity of preclinical research to support this concept. The validity of db/db mouse as an animal model to study type-2 diabetes and related complications is known. The present study was designed to investigate comprehensively the db/db mouse behavior as preclinical evidence of type-2 diabetes related major neurobehavioral complications. We tested juvenile (5–6 weeks) and adult (10–11 weeks) db/db mice for behavioral depression in forced swim test (FST), psychosis-like symptoms using pre-pulse inhibition (PPI) test, anxiety behavior employing elevated plus maze (EPM) test, locomotor behavior and thigmotaxis using open field test and working memory deficits in Y-maze test. Both juvenile and adult group db/db mice displayed behavioral despair with increased immobility time in FST. There was an age-dependent progression of psychosis-like symptoms with disrupted PPI in adult db/db mice. In the EPM test, db/db mice were less anxious as observed by increased percent open arms time and entries. They were also hypolocomotive as evident by a decrease in their basic and fine movements. There was no impairment of working memory in the Y-maze test in db/db mice. This is the first report of depression, psychosis-like symptoms and anxiolytic behavior of db/db mouse strain. It is tempting to speculate that this mouse strain can serve as useful preclinical model to study type-2 diabetes related neurobehavioral complications.

Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

“…In addition to the association between diabetes and accelerated cognitive decline, there is growing support for a link between diabetes and mood disorders, especially depression (24)(25)(26). The mechanisms by which T2D influences depression are not known, but insulin resistance states are associated with increased inflammation and cytokine production in some brain regions (27,28).…”

Possible role of the dopamine D1 receptor in the sensorimotor gating deficits induced by high-fat diet

“…Notably, the db/db mouse Electronic supplementary material The online version of this article (doi:10.1007/s00213-015-4068-x) contains supplementary material, which is available to authorized users. also exhibited PPI disruption (Sharma et al 2010). These results suggest that the obesity phenotype may be related to schizophrenia-like behavioral abnormalities.…”

Triazolam Impairs Avoidance Reaction-A Scientific Proof Why the Victim does not Escape from Drug-Facilitated Sexual Assaults

“…Because placing a rodent on an elevated fenceless open arm is actually inducing a crisis situation or fear for the rodent, and where the anxious behavior is reflected by decreased locomotor activity in the open arm (duration and/or number of entries) and vice versa [18][19][20][21][22][23][24][25][26]. In nature, rodents prefer dark enclosed spaces (it is the enclosed arm in this case) with walls to open areas.…”

“…The elevated plus-maze test, which has been successfully used for the screening of potential anxiolytics, has previously been described [18][19][20][21][22][23][24][25][26]. The explanation of the behavior of rodents in the elevated maze is that exposure to novel stimuli (in the form of maze arms) can evoke both exploratory and fear-driven tendencies, thus generating approach-avoidance conflict behavior, and the elevated maze arms evoke a greater level of fear in the open arms (and therefore more avoidance behavior) than enclosed arms [18].…”