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  • Title: Improved Stress Control in Serotonin Transporter Knockout Rats: Involvement of the Prefrontal Cortex and Dorsal Raphe Nucleus.
    Author: Schipper P, Lopresto D, Reintjes RJ, Joosten J, Henckens MJ, Kozicz T, Homberg JR.
    Journal: ACS Chem Neurosci; 2015 Jul 15; 6(7):1143-50. PubMed ID: 26132384.
    Abstract:
    Variations in serotonin transporter (5-HTT) expression have been associated with altered sensitivity to stress. Since controllability is known to alter the impact of a stressor through differential activation of the medial prefrontal cortex (mPFC) and dorsal raphe nucleus (DRN), and that these regions are functionally affected by genetic 5-HTT down-regulation, we hypothesized that 5-HTT expression modulates the effect of controllability on stressor impact and coping. Here, we investigated the effects of a signaled stress controllability task or a yoked uncontrollable stressor on behavioral responding and mPFC and DRN activation. 5-HTT(-/-) rats proved better capable of acquiring the active avoidance task than 5-HTT(+/+) animals. Controllability determined DRN activation in 5-HTT(+/+), but not 5-HTT(-/-), rats, whereas controllability-related activation of the mPFC was independent of genotype. These findings suggest that serotonergic activation in the DRN is involved in stress coping in a 5-HTT expression dependent manner, whereas mPFC activation seems to be implicated in control over stress independently of 5-HTT expression. We speculate that alterations in serotonergic feedback in the DRN might be a potential mechanism driving this differential stress coping.
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