P49 Novel marine compounds — antitumor or genotoxic: Role of endpoint biomarkers

Abstract

We investigated the immediate and lasting effect of social instability stress in adolescence [SS: daily 1 h isolation and change of cage partner postnatal days (P) 30–45] on cell proliferation in the hippocampus and on spatial memory using an object spatial location (SL) test. Female rats were treated with bromodeoxyuridine (BrdU) P43–45, and on P49, SS had reduced cell hippocampal cell proliferation/survival compared to controls as indicated by BrdU immunoreactive cell counts (p = 0.009), and did not differ in Ki67 immunoreactive cell counts (p = 0.15) from CTL. A separate group of SS and CTL rats were tested at P47 and P48, and again at P72 and P73 on the SL test using 1 and 8 h retention intervals. SS and CTL females did not differ in adolescence, but CTL had better memory than SS as adults (p = 0.03). The better memory performance of CTL rats is not due to differential investigation of objects during the familiarization pre-tests or by differential locomotor activity. The lasting memory reduction and reduced cell proliferation/survival in SS rats is consistent with the hypothesis that ongoing development of the hippocampus renders the adolescent particularly vulnerable to chronic social stress.