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Abstract
It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS), to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA) in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.
Highlights
Depression, with 10 to 20% lifetime prevalence, is the most common psychiatric illness that involves the disturbance of mood [1]
We aimed to use the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to investigate whether the hippocampal volume and neurochemical changes would be related to the learning and memory changes induced by chronic unpredictable mild stress (CUMS) or escitalopram treatment in a rat model of CUMS
Post-hoc analysis showed that the sucrose preference of CUMS+saline animals was significantly decreased compared with control+saline rats (P,0.05), and this was reversed by chronic escitalopram administration (P,0.05) (Fig. 1A)
Summary
Depression, with 10 to 20% lifetime prevalence, is the most common psychiatric illness that involves the disturbance of mood [1]. It is becoming increasingly clear that disturbances in cognitive processes, especially the impairment of learning and memory ability, play an important role in the development and maintenance of depression [2,3,4,5,6]. The hippocampus is a brain structure that has been extensively studied with regard to stress, depression and the effects of antidepressants. Functional neuroimaging studies of depressed individuals have identified abnormalities of resting blood flow and glucose metabolism in the hippocampus and brain regions that are extensively connected to it [11]. To further our understanding of this evidence, it is very important to investigate whether stress-induced functional and morphological changes in the hippocampus are correlated with impairments in learning and memory in depression
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