title: Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague-Dawley rats.
abstract: Selective serotonin reuptake inhibitors (SSRIs) block the serotonin (5-HT) reuptake transporter (SERT) and increase synaptic 5-HT. 5-HT is also important in brain development; hence when SSRIs are taken during pregnancy there exists the potential for these drugs to affect CNS ontogeny. Prenatal SSRI exposure has been associated with an increased prevalence of autism spectrum disorder (ASD), and peripheral 5-HT is elevated in some ASD patients. Perinatal SSRI exposure in rodents has been associated with increased depression and anxiety-like behavior, decreased sociability, and impaired learning in the offspring, behaviors often seen in ASD. The present study investigated whether perinatal exposure to citalopram causes persistent neurobehavioral effects. Gravid Sprague-Dawley rats were assigned to two groups and subcutaneously injected twice per day with citalopram (10mg/kg; Cit) or saline (Sal) 6h apart on embryonic day (E)6-21, and then drug was given directly to the pups after delivery from postnatal day (P)1-20. Starting on P60, one male/female from each litter was tested in the Cincinnati water maze (CWM) and open-field before and after MK-801. A second pair from each litter was tested in the Morris water maze (MWM) and open-field before and after (+)-amphetamine. A third pair was tested as follows: elevated zero-maze, open-field, marble burying, prepulse inhibition of acoustic startle, social preference, and forced swim. Cit-exposed rats were impaired in the MWM during acquisition and probe, but not during reversal, shift, or cued trials. Cit-exposed rats also showed increased marble burying, decreased time in the center of the open-field, decreased latency to immobility in forced swim, and increased acoustic startle across prepulse intensities with no effects on CWM. The results are consistent with citalopram inducing several ASD-like effects. The findings add to concerns about use of SSRIs during pregnancy. Further research on different classes of antidepressants, dose-effect relationships, timing of exposure periods, and mechanisms for these effects are needed. It is also important to balance the effects described here against the effects of the disorders for which the drugs are given.
authors: Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, United States. Electronic address: jenna.sprowles@cchmc.org.
authors: Jenna L N
authors: JL
authors: Sprowles
authors: Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, United States; University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States. Electronic address: jillian.hufgard@cchmc.org.
authors: Jillian R
authors: JR
authors: Hufgard
authors: Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, United States; University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States. Electronic address: Arnold.gutierrez@cchmc.org.
authors: Arnold
authors: A
authors: Gutierrez
authors: Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, United States; University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States. Electronic address: Rebecca.bailey@cchmc.org.
authors: Rebecca A
authors: RA
authors: Bailey
authors: Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, United States. Electronic address: sarah.jablonski@cchmc.org.
authors: Sarah A
authors: SA
authors: Jablonski
authors: Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, United States; University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States. Electronic address: Michael.williams@cchmc.org.
authors: Michael T
authors: MT
authors: Williams
authors: Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH, United States; University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States. Electronic address: Charles.vorhees@cchmc.org.
authors: Charles V
authors: CV
authors: Vorhees
mesh_terms: D000367:Age Factors; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced*; D001835:Body Weight / Q000187:drug effects; D015283:Citalopram / Q000633:toxicity*; D003863:Depression / Q000139:chemically induced*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055139:Sensory Gating / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*; D012737:Sex Factors; D065853:Spatial Learning / Q000187:drug effects*; D013550:Swimming / Q000523:psychology
chemical_list: D000662:Amphetamines; D015283:Citalopram; D016291:Dizocilpine Maleate; D018696:Neuroprotective Agents; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressant; Autism-related behavior; Citalopram; Developmental neurotoxicity; Rat; SSRI