TY - JOUR
T1 - Early-life exposure to selective serotonin reuptake inhibitors: Long-term effects on pain and affective comorbidities
AU - Baudat, M.
AU - de Kort, A.R.
AU - van den Hove, D.L.A.
AU - Joosten, E.A.
N1 - Funding Information:
M.B. is financially supported by the the Pain Knowledge Center from Maastricht.
Publisher Copyright:
© 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
PY - 2022/1
Y1 - 2022/1
N2 - A growing body of evidence indicates that early-life exposure to selective serotonin reuptake inhibitor has long-term consequences on the offspring's pain in addition to affective disorders like anxiety disorder and major depression. Serotonin, besides its role in regulating pain and emotions, promotes neuronal network formation. The prefrontal cortex and the amygdala are two key brain regions involved in the modulation of pain and its affective comorbidities. Thus, the aim of this review is to understand how early-life selective serotonin reuptake inhibitor exposure alters the developing prefrontal cortex and amygdala and thereby underlies the long-term changes in pain and its affective comorbidities in later life. While there is still limited data on the effects of early-life selective serotonin reuptake inhibitor exposure on pain, there is a substantial body of evidence on its affective comorbidities. From this perspective paper, four conclusions emerged. First, early-life selective serotonin reuptake inhibitor exposure results in long-term nociceptive effects, which needs to be consistently studied to clarify. Second, it results in enhanced depressive-like behaviour and diminished exploratory behaviour in adult rodents. Third, early-life selective serotonin reuptake inhibitor exposure alters serotonergic levels, transcription factors expression, and brain-derived neurotrophic factor levels, resulting in hyperconnectivity within the amygdala and the prefrontal cortex. Finally, it affects antinociceptive inputs of the prefrontal cortex and the amygdala in the spinal cord. We conclude that early-life selective serotonin reuptake inhibitor exposure affects the maturation of prefrontal cortex and amygdala circuits and thereby enhances their antinociceptive inputs in the spinal cord.
AB - A growing body of evidence indicates that early-life exposure to selective serotonin reuptake inhibitor has long-term consequences on the offspring's pain in addition to affective disorders like anxiety disorder and major depression. Serotonin, besides its role in regulating pain and emotions, promotes neuronal network formation. The prefrontal cortex and the amygdala are two key brain regions involved in the modulation of pain and its affective comorbidities. Thus, the aim of this review is to understand how early-life selective serotonin reuptake inhibitor exposure alters the developing prefrontal cortex and amygdala and thereby underlies the long-term changes in pain and its affective comorbidities in later life. While there is still limited data on the effects of early-life selective serotonin reuptake inhibitor exposure on pain, there is a substantial body of evidence on its affective comorbidities. From this perspective paper, four conclusions emerged. First, early-life selective serotonin reuptake inhibitor exposure results in long-term nociceptive effects, which needs to be consistently studied to clarify. Second, it results in enhanced depressive-like behaviour and diminished exploratory behaviour in adult rodents. Third, early-life selective serotonin reuptake inhibitor exposure alters serotonergic levels, transcription factors expression, and brain-derived neurotrophic factor levels, resulting in hyperconnectivity within the amygdala and the prefrontal cortex. Finally, it affects antinociceptive inputs of the prefrontal cortex and the amygdala in the spinal cord. We conclude that early-life selective serotonin reuptake inhibitor exposure affects the maturation of prefrontal cortex and amygdala circuits and thereby enhances their antinociceptive inputs in the spinal cord.
KW - affective disorders
KW - amygdala
KW - early-life
KW - pain
KW - prefrontal cortex
KW - selective serotonin reuptake inhibitors
KW - NEONATAL FLUOXETINE EXPOSURE
KW - HIPPOCAMPAL BDNF GENE
KW - PRENATAL STRESS
KW - PERINATAL FLUOXETINE
KW - DEVELOPMENTAL FLUOXETINE
KW - FUNCTIONAL CONNECTIVITY
KW - ANTIDEPRESSANT EXPOSURE
KW - 5-HT TRANSPORTER
KW - SSRI EXPOSURE
KW - RAT-BRAIN
U2 - 10.1111/ejn.15544
DO - 10.1111/ejn.15544
M3 - (Systematic) Review article
C2 - 34841582
SN - 0953-816X
VL - 55
SP - 295
EP - 317
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 1
ER -