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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1143-1150 |
| Number of pages | 8 |
| Journal | ACS Chemical Neuroscience |
| Volume | 6 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 15 2015 |
| Externally published | Yes |
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Keywords
- avoidance
- controllability
- dorsal raphe nucleus
- Serotonin
- serotonin transporter
- stress
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Cognitive Neuroscience
- Cell Biology
Cite this
Improved Stress Control in Serotonin Transporter Knockout Rats : Involvement of the Prefrontal Cortex and Dorsal Raphe Nucleus. / Schipper, Pieter; Lopresto, Dora; Reintjes, Roy J.; Joosten, Joep; Henckens, Marloes J.A.G.; Kozicz, Tamas; Homberg, Judith R.
In: ACS Chemical Neuroscience, Vol. 6, No. 7, 15.07.2015, p. 1143-1150.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=84937044753&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937044753&partnerID=8YFLogxK
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 -