TY - JOUR
T1 - Perinatal vs Genetic Programming of Serotonin States Associated with Anxiety
AU - Altieri, Stefanie C.
AU - Yang, Hongyan
AU - O'Brien, Hannah J.
AU - Redwine, Hannah M.
AU - Senturk, Damla
AU - Hensler, Julie G.
AU - Andrews, Anne M.
N1 - Funding Information:
Support from the National Institute of Mental Health (MH064756, MH086108), the Brain and Behavior Research Foundation (formerly NARSAD), the Shirley and Stefan Hatos Foundation, and the UCLA Weil Endowment Fund are gratefully acknowledged. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. During the past 2 years, AMA has received compensation from Forest Laboratories (Actavis) as a consultant, in addition to income from primary employers. The remaining authors declare that, except for income received from primary employers, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior.
AB - Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior.
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U2 - 10.1038/npp.2014.331
DO - 10.1038/npp.2014.331
M3 - Article
C2 - 25523893
AN - SCOPUS:84939787582
VL - 40
SP - 1456
EP - 1470
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 6
ER -