title: Cognitive impairments from developmental exposure to serotonergic drugs: citalopram and MDMA.
abstract: We previously showed that developmental 3,4-methylenedioxymethamphetamine (MDMA) treatment induces long-term spatial and egocentric learning and memory deficits and serotonin (5-HT) reductions. During brain development, 5-HT is a neurotrophic factor influencing neurogenesis, synaptogenesis, migration, and target field organization. MDMA (10 mg/kg × 4/d at 2 h intervals) given on post-natal day (PD) 11-20 in rats (a period of limbic system development that approximates human third trimester brain development) induces 50% reductions in 5-HT during treatment and 20% reductions when assessed as adults. To determine whether the 5-HT reduction is responsible for the cognitive deficits, we used citalopram (Cit) pretreatment to inhibit the effects of MDMA on 5-HT reuptake in a companion study. Cit attenuated MDMA-induced 5-HT reductions by 50% (Schaefer et al., 2012). Here we tested whether Cit (5 or 7.5 mg/kg × 2/d) pretreatment attenuates the cognitive effects of MDMA. Within each litter, different offspring were treated on PD11-20 with saline (Sal) + MDMA, Cit + MDMA, Cit + Sal or Sal + Sal. Neither spatial nor egocentric learning/memory was improved by Cit pretreatment. Unexpectedly, Cit + Sal (at both doses) produced spatial and egocentric learning deficits as severe as those caused by Sal + MDMA. These are the first data showing cognitive deficits resulting from developmental exposure to a selective serotonin reuptake inhibitor. These data indicate the need for further research on the long-term safety of antidepressants during pregnancy.
authors: Division of Child Neurology, Department of Pediatrics, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
authors: Tori L
authors: TL
authors: Schaefer
authors: Curtis E
authors: CE
authors: Grace
authors: Amanda A
authors: AA
authors: Braun
authors: Robyn M
authors: RM
authors: Amos-Kroohs
authors: Devon L
authors: DL
authors: Graham
authors: Matthew R
authors: MR
authors: Skelton
authors: Michael T
authors: MT
authors: Williams
authors: Charles V
authors: CV
authors: Vorhees
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D015283:Citalopram / Q000633:toxicity*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018490:Serotonin Agents / Q000633:toxicity*; D013550:Swimming / Q000523:psychology
chemical_list: D018490:Serotonin Agents; D015283:Citalopram; D018817:N-Methyl-3,4-methylenedioxyamphetamine