Formula omitted]-Cycloserine: Effects on Long-Term Retention of a Conditioned Response and on Memory for Contextual Attributes

Abstract

d-Cycloserine (DCS), a partial agonist of the glycine recognition site of the N-methyl d-aspartate receptor, has beneficial effects on learning and memory. In order to investigate its potential to influence learning and memory of both the response and the stimulus attributes of training, male Sprague-Dawley albino rats were trained in a one-trial inhibitory avoidance task following an acute intraperitoneal injection of DCS (3 mg/kg) or an equal volume of saline. In order to measure memory for stimulus attributes, testing involved a context shift paradigm, in which subjects are tested in either the environment of training or a different one. Good memory for the contextual attributes of training is indicated by poor performance in the alternate context. Retention was assessed either 1, 7, or 14 days after training. At 1 day, Saline subjects were affected by a change in context, while DCS subjects were not. In subjects tested 1 week following training, Saline subjects were no longer affected by a change in context, in that they performed the avoidance response in both contexts. This indicates the forgetting of stimulus attributes in Saline subjects. DCS subjects did show the context shift effect at 1 week, indicating the retention of stimulus attributes. Finally, Saline subjects demonstrated the context shift rebound at 14 days, while DCS subjects performed equivalently in both contexts. Taken together, these data suggest that DCS may enhance retention of fear and slow the forgetting of stimulus attributes.