Cognitive impairments from developmental exposure to serotonergic drugs citalopram and MDMA.
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 mgkg × 4d 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 mgkg × 2d) 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 learningmemory 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.