Escapable stress modulates retention of spatial learning in rats: Preliminary evidence for involvement of neurosteroids

Abstract

The ability to escape stress has been shown to protect an organism from many of the deleterious effects of stress exposure. It has been suggested that this amelioration could be mediated by the release of an endogenous benzodiazepine-like substance in the brain demonstrated 2 h poststress. Since benzodiazepines possess amnestic as well as antianxiety actions, the possibility of memory alterations in coping subjects was evaluated. Animals were randomly assigned to three groups: escapable shock, yoked inescapable shock, and no shock. Immediately poststress, all subjects were trained in a circular water maze. Acquisition and retention data were obtained in a between-subjects design at three different retention intervals (2 h, 4 h, and 24 h postshock). Results revealed no significant group differences in acquisition of the spatial learning task between groups. However, subjects in the escapable stress group had enhanced retention at 2 h postshock but were significantly impaired 24 h postshock relative to yoked-inescapable-shock and nonshock controls. Blockade of the synthesis of neuroactive GABA(A) positive steroids by 4-MA, a 5-alpha reductase enzyme inhibitor, blocked this effect. Thus, neuroactive steroid metabolites may play a critical role in the escapable stress-induced retention deficit seen at 24 h poststress. These observations suggest that altered memory in the escapable-shock subjects may impart stress resiliency by reducing proactive interference of prior stress on subsequent learning and physiology.