title: Perinatal vs genetic programming of serotonin states associated with anxiety.
abstract: 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.
authors.affiliation: 1] Semel Institute for Neuroscience and Human Behavior and Hatos Center for Neuropharmacology, David Geffen School of Medicine, and California NanoSystems Institute, University of California, Los Angeles, CA, USA [2] Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Altieri
authors.affiliation: Semel Institute for Neuroscience and Human Behavior and Hatos Center for Neuropharmacology, David Geffen School of Medicine, and California NanoSystems Institute, University of California, Los Angeles, CA, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Semel Institute for Neuroscience and Human Behavior and Hatos Center for Neuropharmacology, David Geffen School of Medicine, and California NanoSystems Institute, University of California, Los Angeles, CA, USA.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: O'Brien
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Redwine
authors.affiliation: Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
authors.forename: Damla
authors.initials: D
authors.lastname: Senturk
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Hensler
authors.affiliation: 1] Semel Institute for Neuroscience and Human Behavior and Hatos Center for Neuropharmacology, David Geffen School of Medicine, and California NanoSystems Institute, University of California, Los Angeles, CA, USA [2] Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Andrews
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001008:Anxiety Disorders / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493231:Slc6a4 protein, mouse