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

Kazuyuki Yamada

doi:10.4236/wjns.2016.62019

Abstract

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 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.

Highlights

Specific Serotonin Reuptake Inhibitors (SSRIs) are generally known to be effective with a relatively low risk ofHow to cite this paper: Yamada, K. (2016) Single Exposure to Antidepressants during Infancy Is Associated with Delayed Behavioral Changes in C57BL/6 Mice
Forty-nine, thirty-nine, and fifty-eight male C57BL/6J mice were used in this study
The hole-board apparatus is a variant of the open field, but has four holes on the floor to explore

Summary

Introduction

Specific Serotonin Reuptake Inhibitors (SSRIs) are generally known to be effective with a relatively low risk ofHow to cite this paper: Yamada, K. (2016) Single Exposure to Antidepressants during Infancy Is Associated with Delayed Behavioral Changes in C57BL/6 Mice. Specific Serotonin Reuptake Inhibitors (SSRIs) are generally known to be effective with a relatively low risk of. The toxic effects of exposure to antidepressants in utero and during lactation have long been studied [4]-[7], it is not known whether long-term behavioral effects are exhibited in adulthood. Chronic exposure to SSRIs to neonates might lead to long lasting effects on behavior. Rodent studies have shown that the sub-chronic administration of SSRIs to neonates increased immobility in the forced swimming test (Lu 10-134-C: [9]), increased locomotor activity, but decreased sexual behavior later in adulthood (citalopram: [10]) as well as a tricyclic antidepressant which preferentially but not selectively inhibits serotonin reuptake (clomipramine: [11])

Methods

Results

Conclusion