D-cycloserine: Effects on long-term retention of a conditioned response and on memory for contextual attributes

D-Cycloserine (DCS), a partial agonist of the glycine! recognition site of the N-methyl D-aspartate receptor, has beneficial effects on learning and m emory. In order to investigate its potential to influence learning and memo ry of both the response and the stimulus attributes of training, male Sprag ue-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, testi ng involved a context shift paradigm, in which subjects are tested in eithe r the environment of training or a different one. Good memory for the conte xtual attributes of training is indicated by poor performance in the altern ate 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 sub jects were no longer affected by a change in context, in that they performe d 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 I week, indicating the retention of stimulus attributes. F inally, 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 for getting Of stimulus attributes. (C) 1999 Academic Press.