LONG-LASTING MNEMOTROPIC EFFECT OF SUBSTANCE-P AND ITS N-TERMINAL FRAGMENT (SP1-7) ON AVOIDANCE-LEARNING

We investigated the long-lasting effect of peripheral injection of the neuropeptide substance P (SP) and of some N- or C-terminal SP fragmen ts (SPN and SPC, respectively) on retention test performance of avoida nce learning. Male Wistar rats (220 to 280 g) were trained in an inhib itory step-down avoidance task and tested 24 h or 21 days later. Immed iately after the training trial rats received an intraperitoneal injec tion of SP (50 mu g/kg), SPN 1-7 (167 mu g/kg) or SPC 7-11 (134 mu g/k g). Control groups were injected with vehicle or SP 5 h after the trai ning trial. The immediate post-training administration of SP and SPN, but not SPC, facilitated avoidance behavior in rats tested 24 h or 21 days later, i.e., the retention test latencies of the SP and SPN group s were significantly longer (P < 0.05, Mann-Whitney U-test) during bot h training-test intervals. These observations suggest that the memory- enhancing effect of SP is long-lasting and that the amino acid sequenc e responsible for this effect is encoded by its N-terminal part.