Opposite strain-dependent effects of post-training corticosterone in a passive avoidance task in mice: role of...

Post-training administration of corticosterone (0.1-1 mg/kg) dose-dependently improves retention of an inhibitory avoidance response in C57BL/6 mice, whilst impairing it in the DBA/2 strain. The effects on retention performance induced by the hormone in C57BL/6 and DBA/2 mice appear to be due to an effect on memory consolidation. In fact, they were observed when the drug was given at short, but not long, periods of time after training, i.e., when the memory trace is susceptible to modulation. In the absence of pharmacological manipulations, the two strains showed a significant increase of plasma corticosterone levels 15 min after passive avoidance training that disappeared within 30 min, and similar step-through latencies on the test day. However, although no strain differences were observed for sensitivity to shock thresholds, the increase in plasma corticosterone levels elicited by passive avoidance training was more pronounced in mice of the DBA/2 strain (+160%) than in C57BL/6 mice (+52%). Moreover, DBA/2 mice were characterised by a higher number of either Type I or Type II corticosteroid receptors in the hippocampus in comparison with C57BL/6 mice. Finally, the strain-dependent effects of an intermediate dose of corticosterone were enhanced by pretreatment with either the selective D1 or D2 dopamine (DA) receptor agonists SKF 38393 and LY 171555 and reversed by pretreatment with either selective D1 or D2 DA receptor antagonists SCH 23390 and (-)-sulpiride administered at per se non-effective doses. The present results indicate that studies in inbred strains of mice can dissect opposite effects of corticosterone on memory consolidation possibly due to its action at different steps or components of the multiphasic pathway of memory consolidation. Moreover, they suggest that some of these steps involve an interaction between the hormone and brain DA system.