Posttraining administration of substance P and its N-terminal fragment block the amnestic effects of diazepam

This study examined the effects of posttraining administration of substance P (SP) and of certain N- or C-terminal SP-fragments on retention performance of rats treated with diazepam (DZP). Twenty minutes before the training on an inhibitory avoidance task rats were given intraperitoneal injections of either DZP (2 mg/kg) or vehicle. Immediately after they were injected with SP (50 mu g/kg), SPN 1-7 (167 mu g/kg), SPC 6-11 (134 mu g/kg), or vehicle. The posttrial administration of SP and SPN, but not SPC, facilitated avoidance behavior. Animals that received DZP before training and vehicle after the conditioning trial showed impaired retention. In contrast, in animals injected with SP and SPN after the training trial, DZP did not affect retention. These findings suggest that the amnestic effects of DZP can be blocked by the administration of SP and that the amino acid sequence responsible for this effect may be encoded by its N-terminal part. (C) 1998 Academic Press.