Stress-Induced Memory Retrieval Impairments: Different Time-Course Involvement of Corticosterone and Glucocorticoid Receptors in Dorsal and Ventral Hippocampus

Abstract

The present study was aimed at determining the relative contribution of the dorsal (DH) and ventral (VH) hippocampus in stress-induced memory retrieval impairments. Thus, we studied the temporal involvement of corticosterone and its receptors, i.e. mineralocorticoid (MR) and glucocorticoid (GR) in the DH and VH, in relation with the time-course evolution of stress-induced memory retrieval impairments. In a first experiment, double microdialysis allowed showing on the same animal that an acute stress (electric footshocks) induced an earlier corticosterone rise in the DH (15–60 min post-stress) and then in the VH (90–105 min post-stress). The return to baseline was faster in the DH (105 min) than in the VH (120 min). Memory deficits assessed by delayed alternation occurred at 15-, 60-, and 105-min delays after stress and were closely related to the kinetic of corticosterone rises within the DH and VH. In a second experiment, the GR antagonist RU-38486 and the MR antagonist RU-28318 were administered in the DH or VH 15 min before stress. RU-38486 restored memory at 60 but not at 105 min post-stress delays in the DH, whereas the opposite pattern was observed in the VH. By contrast, RU-28318 had no effect on memory impairments at both the 60- and 105-min post-stress delays, showing that MR receptors are not involved at these delays. However, RU-28318 administered in the DH restored memory when administered at a shorter post-stress delay (15 min). Overall, our data are first to evidence that stress induces a functional switch from the DH to VH via different corticosterone time-course evolutions in these areas and the sequential GR receptors involvement in the DH and then in the VH, as regards the persistence of stress-induced memory retrieval deficits over time.

Blocking Mineralocorticoid Receptors Impairs, Blocking Glucocorticoid Receptors Enhances Memory Retrieval in Humans

“…In contrast, blockade of GRs in the present study enhanced free recall of pictures, with an equivalent effect for neutral and emotional picture details. This finding is consistent with animal studies that report GR blockade to abolish the memory retrieval impairment in animals with high hippocampal corticosterone levels (Yau et al , 2011; Dorey et al , 2012). Also, another rodent study suggested an enhancing effect after continuous administration of a GR blocker on retrieval of spatial memory (Oitzl et al , 1998).…”

Ventral hippocampus, Stress and Psychopathology: Translational implications

“…Dorey et al [17] studied the relative contribution of the DH and VH in stress induced memory retrieval impairments, specifically, the temporal involvement of corticosterone and its receptors, MRs and GRs. The results of the study suggest that stress induces a func tional switch from the DH to VH via different corti costerone time course evolutions in these areas and the sequential GRs involvement in the DH and later in the VH.…”

Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress

“…Dialysate levels were not corrected for differences in probe recovery. To account for this, dialysate levels were expressed as the % of the average of the baseline samples (Barr et al, 2013; Dorey et al, 2012; Droste et al, 2008, 2009a; Keeney et al, 2006; Li et al, 2014). …”