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- Title
Emotional memory impairments in a genetic rat model of depression: involvement of 5-HT/MEK/Arc signaling in restoration.
- Authors
Eriksson, T M; Delagrange, P; Spedding, M; Popoli, M; Mathé, A A; Ögren, S O; Svenningsson, P
- Abstract
Cognitive dysfunctions are common in major depressive disorder, but have been difficult to recapitulate in animal models. This study shows that Flinders sensitive line (FSL) rats, a genetic rat model of depression, display a pronounced impairment of emotional memory function in the passive avoidance (PA) task, accompanied by reduced transcription of Arc in prefrontal cortex and hippocampus. At the cellular level, FSL rats have selective reductions in levels of NMDA receptor subunits, serotonin 5-HT1A receptors and MEK activity. Treatment with chronic escitalopram, but not with an antidepressant regimen of nortriptyline, restored memory performance and increased Arc transcription in FSL rats. Multiple pharmacological manipulations demonstrated that procognitive effects could also be achieved by either disinhibition of 5-HT1AR/MEK/Arc or stimulation of 5-HT4R/MEK/Arc signaling cascades. Taken together, studies of FSL rats in the PA task revealed reversible deficits in emotional memory processing, providing a potential model with predictive and construct validity for assessments of procognitive actions of antidepressant drug therapies.
- Subjects
MENTAL depression; LABORATORY rats; MEMORY; PREFRONTAL cortex; HIPPOCAMPUS (Brain)
- Publication
Molecular Psychiatry, 2012, Vol 17, Issue 2, p173
- ISSN
1359-4184
- Publication type
Article
- DOI
10.1038/mp.2010.131