TY - JOUR
T1 - Improved Stress Control in Serotonin Transporter Knockout Rats
T2 - Involvement of the Prefrontal Cortex and Dorsal Raphe Nucleus
AU - Schipper, Pieter
AU - Lopresto, Dora
AU - Reintjes, Roy J.
AU - Joosten, Joep
AU - Henckens, Marloes J.A.G.
AU - Kozicz, Tamas
AU - Homberg, Judith R.
PY - 2015/7/15
Y1 - 2015/7/15
N2 - 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.
AB - 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.
KW - avoidance
KW - controllability
KW - dorsal raphe nucleus
KW - Serotonin
KW - serotonin transporter
KW - stress
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U2 - 10.1021/acschemneuro.5b00126
DO - 10.1021/acschemneuro.5b00126
M3 - Article
C2 - 26132384
AN - SCOPUS:84937044753
VL - 6
SP - 1143
EP - 1150
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
SN - 1948-7193
IS - 7
ER -