Sertraline exposed mice had significantly increased weights during the neonatal exposure compared to control mice (Physique 1A, N= 14 sertraline, 14 saline). of multiple 5-HT receptors, serotonin transporter (5-HTT), and tryptophan hydroxylase isoform 2 in the cerebral cortex. Conclusion: Although no behavioral phenotype was observed, SSRI exposure in the perinatal period permanently alters cerebral receptor mRNA levels. We speculate these shifts in mRNA expression provide important compensation during SSRI exposure. Further pre-clinical and clinical investigation into additional serotonin-regulated phenotypes is necessary to further assess the long-term implications of perinatal SSRI TTA-Q6 exposure. value of 0.05 was considered significant. TTA-Q6 To correct for multiple comparisons, Bonferroni correction was performed and em p /em 0.007 was considered significant for cortex PDGF1 mRNA expression. Results Exposure Model. Dam weights at initiation of breeding were not different. Sertraline uncovered mice had significantly increased weights during the neonatal exposure compared to control mice (Physique 1A, N= 14 sertraline, 14 saline). Sertraline levels in pups at the end of 14 days were 10 ng/mL (N=8), consistent with umbilical levels in humans . There were no differences in weights at the time of weaning (PN day 21) or at 20 weeks of age (time of behavioral testing) between the control mice and sertraline-exposed mice (Physique 1B, and 1C, respectively, N= 22 sertraline, 20 saline). The cerebral cortex weights were not different between the groups (sertraline 250 4 mg, saline 249 4 mg, p=0.87, N= 27 sertraline, 32 saline). No sex differences were observed between the two groups. Open in a separate window TTA-Q6 Physique 1. Body weights on (A) postnatal days 1C14, (B) day 21, and (C) 20 weeks of age for sertraline-exposed and control mice. Social Interaction. There was no significant difference between groups in the average time spent in either chamber or in the amount of time sniffing the stranger mouse versus time sniffing the vacant enclosure (Physique 2A, N= 24 sertraline, 23 saline). Open in a separate window Physique 2. Behavioral testing of sertraline-exposed and control mice including A) interpersonal interactions in tripartite chamber, B) stress/fear in elevated plus maze, and C) spatial learning in Barnes maze. Stress/Fear Response. No differences were noted between the groups in the amount of time spent in the open arm versus closed arm of the elevated plus maze (Physique 2B, N=24 sertraline, 23 saline). Spatial Learning. No significant differences were noted in spatial learning between the groups on any of the testing days (Physique 2C, N= 24 sertraline, 23 saline). The time to find the escape hole improved from the baseline on days 3, 4, and 5 for both groups. When the escape hole was in a different location (day 5 reverse), sertraline mice tended to find the escape hole faster than control mice (Day 5 Reverse: sertraline 113.0 17.6 s, saline 157.6 20.4 s, p=0.10). Serotonin transporter protein and serotonin receptor mRNA levels. Perinatal sertraline exposure led to a significant increase in cerebral TTA-Q6 cortex 5-HT1A and 5-HTT mRNA levels compared to control mice (Physique 3A and 3B, N= 27 sertraline, 29 saline). Significant increases were also detected in cerebral cortex 5-HT2A, 5-HT2C, and tryptophan hydroxylase isoform 2 (TPH2) (Physique 3C, 3E, and 3G, N= 17 sertraline, 19 saline). No differences were detected in cerebral cortex mRNA levels of 5-HT2B or TPH1 (Physique 3D and 3F, N=17 sertraline, 19 saline), in both cases, this was associated with low levels of mRNA expression (CT values of 29 and 27, respectively). Open in a separate window Physique 3. Expression levels of cortex 5-HT receptors, the serotonin transporter (5-HTT), and tryptophan hydroxylase 2 in.