Vol. 283, Issue 3, 1333-1341, 1997

Neonatal Administration of the Selective Serotonin Reuptake Inhibitor Lu 10-134-C Increases Forced Swimming-Induced Immobility in Adult Rats: A Putative Animal Model of Depression?

H. H. Hansen, C. Sánchez and E. Meier

Pharmacological Research, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Copenhagen-Valby, Denmark

Chronic administration of the tricyclic antidepressant clomipramine to neonatal rats from postnatal days 8 to 21 is reported to induce several behavioral changes in adult life, and it may serve as an animal model of human depressive disorder. Findings include increased immobility time in the forced swim test and locomotor hyperactivity in the open field test. Clomipramine is a serotonergic reuptake inhibitor, which suggests that altered development of the serotonergic system could account for the observed behavioral changes in the adult rat. The present study was carried out with a selective serotonin reuptake inhibitor (SSRI) to investigate whether the serotonin system, in particular, is involved in the neonatal animal model. The substance, Lu 10-134-C (LU), was characterized in monoamine reuptake and receptor binding assays and found to be an SSRI. Rats received LU during postnatal days 8 to 21 (2.5-15 mg/kg b.i.d.), and they were assessed in open field, forced swim and social interaction tests at the age of 4 months. Behavior of LU-treated rats and saline controls did not differ in the open field and social interaction tests. However, in the forced swim tests LU-treated neonates showed prolonged immobility time compared with saline controls. In conclusion, chronic LU treatment during neonatal life produces long-term changes in the forced swim test, but not in the open field and social interaction tests. The behavioral changes in the forced swim test suggest that the central serotonergic system may be involved in the putative neonatal animal model of depression.