Single Exposure to Antidepressants during Infancy Is Associated with Delayed Behavioral Changes in C57BL/6 Mice

Kazuyuki Yamada
2016 World Journal of Neuroscience  
As serotoninergic transmission plays a crucial role in higher brain function in mammals, the disturbance of this system will likely have significant effects on emotion and cognition. Previous studies have reported that chronic treatment with Specific Serotonin Reuptake Inhibitors (SSRIs) during both late pregnancy and lactation was associated with abnormal behavior in adult rats. These data imply that disturbances in serotoninergic transmission during neurodevelopment may have negative effects
more » ... e negative effects on both the structure and function of the resultant adult brain. Therefore, the effect of a single exposure to an SSRI or a tricyclic antidepressant that preferentially inhibits serotonin reuptake during the pre-weaning period was examined in adult mice. An oral infusion of paroxetine (70 mg/kg), fluvoxamine (250 mg/kg), clomipramine (180 mg/kg), or saline was administered on postnatal day 14. Starting at 11 weeks of age, mice were assessed using a comprehensive behavioral test battery. Mice treated with paroxetine demonstrated altered behavior on the open field and hole-board tasks; those treated with fluvoxamine had behavioral changes on the light-dark box, hole-board, and sucrose preference tasks, while alteration in forced swimming and cued fear behavior were noted in mice treated with clomipramine. These results suggest that even a single administration of an antidepressant could have profound effects on behavior in adulthood, although the effects might differ dependent on the specific drug that was administered. Keywords Antidepressants, Specific Serotonin Reuptake Inhibitors (SSRIs), Delayed Effect, Behavioral Test Battery, Mice Drugs Paroxetine hydrochloride (LKT Laboratories, MN, USA; 70 mg/kg), fluvoxamine maleate (TRC, Ontario, Canada; 250 mg/kg), and clomipramine hydrochloride (SIGMA, MO, USA; 180 mg/kg) were used in this study. All drugs were dissolved at room temperature in physiological saline before behavioral testing. The selected doses were determined by previously conducted pilot experiments to determine safe and efficacious doses of each of the experimental treatments. On postnatal day 14, each animal was administered either the drug or saline orally (per os; P.O.) through a stainless-steel cannula (Muromachi-kikai, Tokyo, Japan) (10 µl/g body weight). Procedure At the age of 11 weeks, behavioral testing began. A three-stage behavioral test battery was used in this study
doi:10.4236/wjns.2016.62019 fatcat:2v5z7nm36jarnlx3n7gr34gyii