Neonatal citalopram exposure produces lasting changes in behavior which are reversed by adult imipramine treatment

Abstract

Neonatal exposure to antidepressants, including selective serotonin reuptake inhibitors such as citalopram, induces behavioral disturbances which persist in mature rats. These disturbances have been proposed to model the symptoms of endogenous depression. However, to date there is scant evidence for the predictive validity of any of these behaviors in response to adult antidepressant treatments. In order to directly assess the predictive validity of the early antidepressant exposure paradigm, the present study examined whether the behavioral abnormalities observed in adult animals exposed as neonates to citalopram can be reversed by adult antidepressant treatment with the prototypic antidepressant, imipramine. As noted earlier, neonatal citalopram exposure robustly increased locomotor activity and impaired male sexual behavior in adult rats. These behavioral changes were reversed following chronic adult imipramine treatment. No such reversal was observed in handled, saline treated rats. The present data support the hypothesis that some of the lasting behavioral abnormalities induced by early antidepressant exposure are sensitive to clinically relevant antidepressant treatments thus adding a measure of predictive validity to this paradigm as a model of these depressive symptoms.

Fig. 1

Effect of chronic administration of saline or imipramine on locomotor activity (upper panel-distance traveled; lower panel-ambulatory time) of rats neonatally exposed to saline or citalopram. Data represents the mean ± S.E.M. of 5–14 rats per group. Two factor analysis of variance followed by Bonferroni test: ^*P<0.05 vs neonatal saline + adult saline; ^**P<0.01 vs neonatal citalopram + adult saline treatment.

Fig. 2

Effect of chronic administration of saline or imipramine on sexual behavior (upper panel-number of mounts; middle panel-number of intromissions; lower panel-number of ejaculations) of rats neonatally exposed to saline or citalopram. Data represents the mean ± S.E.M. of 5–13 rats per group. Two factor analysis of variance followed by Bonferroni test, ^*P<0.05 vs neonatal saline + adult saline treatment.