The sex-specific effects of an antidepressant treatment on cognition in aged rats

Project: Research project

Project Details


The sex-specific effects of an antidepressant treatment on cognition in aged rats The sex-specific effects of an antidepressant treatment on cognition in aged rats Aging and the menopausal transition are each associated with cognitive impairment, which is often co-morbid with affective disorders such as depression and anxiety. Accumulating evidence indicates that decreased serotonin (5-HT) function is associated with a wide range of cognitive disorders, severity of Alzheimers Disease (AD), and affective disorders. Notably, postmenopausal women exhibit decreased serotonergic activity, which is related to a higher incidence of affective and cognitive disorders and both are often effectively treated by selective serotonin reuptake inhibitors (SSRIs), which are a class of antidepressants that enhance 5-HT neurotransmission. The serotonergic neurons in the dorsal raphe nucleus (DRN) are a major source of 5-HT in the forebrain. In particular, polymorphisms of tryptophan hydroxylase-2 (TpH2, the brain specific, rate limiting enzyme for 5-HT biosynthesis) that result in loss of function are implicated in affective disorders and a wide spectrum of cognitive disorders6, suggesting that TpH2 plays an important role in both affect and cognition. In animal studies, SSRIs have been shown to increase TpH2 mRNA in the DRN. Thus, the goal of this application is to determine the effects of the SSRI citalopram on DRN TpH2 expression and on a battery of tasks testing cognitive, depressive-like, and anxiety-like behaviors in male versus female middleaged rats. Animals will be administered citalopram (10 mg/kg, p.o.) in their drinking water starting at 12 months old; control animals will receive water. Starting at 16 months old, animals will be measured in a battery of behaviors, in the following order: open field test (OFT, anxietylike behavior), Object Recognition (OR, visual memory), Object Placement (OP, spatial memory), Water Radial Arm Maze (WRAM, spatial working and reference memory), Morris Water Maze (MWM, spatial reference memory), Delayed Match-to-Sample (DMS, spatial working memory), and Forced Swim Test (FST, despair-like behavior). Then, the brains will be removed, frozen, processed and analyzed for TpH2 mRNA in the DRN, using quantitative RTPCR .
Effective start/end date9/16/139/15/14


  • Institute for Mental Health Research: $20,000.00


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