The involvement of ERK/CREB/Bcl-2 in depression-like behavior in prenatally stressed offspring rats

• PS induced depression-related behavior in juvenile offspring rats.
• PS decreased expression of ERK2, CREB and Bcl-2 mRNA in hippocampus and prefrontal ortex of juvenile offspring rats.
• MK-801 given to dam produced antidepressant-like effects in PS juvenile offspring rats.
• MK-801 given to dam increased expression of ERK2, CREB and Bcl-2 mRNA in hippocampus and prefrontal cortex in PS juvenile offspring rats.

A number of studies reveal that prenatal stress (PS) may induce an increased vulnerability to depression in offspring. Some evidences indicate that extracellular signal-regulated kinase (ERK)-cyclic AMP responsive element binding protein (CREB) signal system may play an important role in the molecular mechanism of depression. In the present study, we examined the effects of prenatal restraint stress on depression-like behavior in one-month offspring Sprague-Dawley rats and expression of ERK2, CREB, B-cell lymphoma-2 (Bcl-2) mRNA in the hippocampus, prefrontal cortex and striatum to explore the potential role of ERK–CREB pathway in mediating the behavioral effects of PS exposure. Our findings demonstrated that PS increased immobility time in forced swimming test and decreased expression of ERK2, CREB, Bcl-2 mRNA in the hippocampus and prefrontal cortex of juvenile offspring rats except for CREB in hippocampus of male offspring. Changes induced by PS were partly prevented by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. These findings suggested that the ERK–CREB system might be related with the depression-like behavior in juvenile offspring rats subjected to PS, in which NMDA receptors might be involved.