The corticosteroid synthesis inhibitors metyrapone and aminoglutethimide impair long-term memory for a passive...

Long-term memory for a passive avoidance task in day-old chicks has proved to depend upon an action of the adrenal steroid corticosterone through specific receptors in a brain region, the intermediate medial hyperstriatum ventrale (IMHV), involved in learning the task. In this study, we questioned whether pretraining peripheral administration of drugs described to inhibit either basal levels of corticosterone - aminoglutethimide - or treatment-induced stimulated corticosterone secretion - metyrapone - might interfere with retention for the task at 24 h post-training. The results showed a dose-dependent effect of the inhibitors, with the highest doses tested for both drugs (10 and 50 mg/kg for metyrapone, and 50 mg/kg for aminoglutethimide) being amnestic for the task. Additional experiments, in which we studied possible effects of the inhibitors on concomitant aspects of learning (i.e., reactivity to novelty, and pecking pattern), show that the drugs did not affect general behavioural reactivity. The present results thus support the idea that training-induced corticosterone release plays a key role in the neurobiological processes that determine the establishment of a persistent memory for the aversively motivated avoidance response. In addition, they point to corticosteroid inhibitor drugs as potential tools for the study of the interactions between steroid hormones and cognition-enhancing compounds in this learning task.