The critical window of brain development from susceptive to insusceptive -Effects of clomipramine neonatal treatment on sexual behavior

The immature brain is much more sensitive to abnormal experience, particula rly sleep deprivation, drug exposure, and maternal separation. The critical time period during which features in the brain's susceptibility to such ex perience change, however, has not yet been determined. In previous studies on rats, we found that neonatal treatment with clomipramine (CLI) during po stnatal days 8-21 (P8-21) produced behavioral and physiological abnormaliti es in adult rats that resembled the abnormalities found in human endogenous depression. The objective of the present study is to determine (1) the cri tical (more specifically, the latest) time frame in which CLI treatment wil l produce adult depression and (2) the shortest treatment window during whi ch CLI can induce adult depression. Male rats were neonatally treated with CLI (20 mg/kg, sc) twice daily or with an equivolume of saline. The treatme nt windows were P12-17, P14-20, P16-22, and P12-15. Six variables, includin g number of mounts, intromission, ejaculation, mount latency, ejaculation l atency, and post-ejaculation interval, were measured visually between the a ges of 4 and 5 months. Rats treated with CLI showed significant sexual impa irment in treatment windows P12-17 and P14-20 and slight sexual deficiency in the short window P12-15. No significant sexual impairment was found in w indow P16-22. We concluded that P14-20 was the latest window during which C LI treatment produces adult sexual deficiency and that 6 days might be the shortest treatment window to produce significant behavior abnormalities. (C ) 2001 Elsevier Science B.V. All rights reserved.