الفهرس 
Cognitive impairment in depressionOnly 14 pages are availabe for public view
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Abstract
BACKGROUND: Major depressive disorder (MDD) is a disabling medical condition associated with significant morbidity, mortality and public health costs. Cognitive deficits in depression represents an important source of functional impairment. Evidences has focused on 5HT7 receptors and its relation to depression and associated cognitive impairment, the role of microglia and Wnt/ β catenin pathway.
5HT7 receptor is a promising target as several studies has shown that the blockade of 5-HT7 receptors by several drugs including amisulpride displays an antidepressant and procognitive effect. Microglia is being accused in the pathogenesis of depression and cognitive impairment, and the Wnt/β catenin pathway is being investigated as a modulator of microglial activity. To the best of our knowledge, no study examined the effect of chronic 5HT7 receptor antagonism on cognitive functions in unpredictable chronic mild stress (UCMS) model of depression or on microglial activity or its relation to the Wnt/β catenin pathway.
Therefore, we conducted this study to investigate the effect of amisulpride on cognitive function of Wistar rats exposed to UCMS as a model of depression. Additionally, in vivo microglial activity and Wnt/β catenin pathway in prefrontal cortex (PFC) will be assessed as a possible mechanism.
Methods: 48 Male Wistar rats were divided into 3 groups: group I: control naïve group; 12 rats, injected with the vehicle (normal saline, 1ml/kg/day) for the last 2 weeks of the experiment. group II: control amisulpride treated group; 12 rats, injected with amisulpride 3mg/Kg/day i.p, for the last 2 weeks of the experiment. group III: UCMS group, 24 rats exposed to UCMS for 6 weeks, further subdivided into a vehicle treated and an amisulpride treated subgroups, 12 rats each. Measured outcomes include: basal and weekly body weight, sucrose preference test, forced swimming test, attentional set shifting task, novel object recognition task and relative weight of adrenal glands. Additionally, microglial activity, markers for the Wnt/β catenin pathway in the PFC were investigated.
Results: UCMS rats exhibited obvious depressive like behaviors (anhedonia, negative alterations in open field and forced swimming test), cognitive impairment (indicated by decreased recognition index in novel object recognition test and increased trials to criterion in attentional set shifting task), decreased body weight gain, increased relative adrenal gland weight, increased microglial activity, increased phosphorylation of beta catenin and decreased levels of total beta catenin, Wnt3a and DVL3 in PFC. Amisulpride significantly attenuated the behavioral, cognitive and neurochemical alterations. These findings imply that amisulpride attenuated UCMS induced depressive like behavior and cognitive impairment through modulation of Wnt/β catenin pathway and microglial activity in prefrontal cortex.