ABSTRACT
We investigated the long-lasting effect of peripheral injection of the neuropeptide substance P (SP) and of some N- or C-terminal SP fragments (SPN and SPC, respectively) on retention test performance of avoidance learning. Male Wistar rats (220 to 280 g) were trained in an inhibitory step-down avoidance task and tested 24 h or 21 days later. Immediately after the training trial rats received an intraperitoneal injection of SP (50 mug/kg), SPN 1-7 (l67 mug/kg) or SPC 7-11 (l34 mug/kg). Control groups were injected with vehicle or SP 5 h after the training 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 groups were significantly longer (P<0.05, Mann-Whitney U-test) during both training-test intervals. These observations suggest that the memory-enhancing effect of SP is long-lasting and that the amino acid sequence responsible for this effect is encoded by its N-terminal part.
Subject(s)
Rats , Animals , Male , Avoidance Learning/drug effects , Memory/drug effects , Substance P/pharmacology , Memory/physiology , Rats, WistarABSTRACT
Experiments were carried out to investigate the effects of peripheral post-training administration of substance P (SP) and naloxone on learning. Rats were trained in three different avoidance tasks (uphill, step-down and alcove) and tested 24 h later. Thirty minutes before each trial (training and testing) rats received naloxone (0.5, 1, 5, or 50 mg/kg, ip) or saline. SP (50 microng/kg) or vehicle was administered ip immediately after training. Animals that received SP and SP in combination with naloxone (5 and 50 mg/kg) showed significantly better retention test performance for the uphill and step-down avoidance (P < 0.05 when compared to control rats treated with vehicle). In the alcove task no influence of SP and/or naloxone was demonstrable, probably due to a ceiling effect. These results suggest that the memory enhancement effects observed are mediated, at least in part, via interactions between substance P and the endogenous opioid systems