Facilitation of memory by peripheral administration of substance P and naloxone using avoidance and habituation...

This paper summarizes results of a series of experiments dealing with the effects of the neuropeptide substance P (SP) on avoidance learning and habituation. Several doses of SP (0.5, 5, 50, 100, 250, 500 micrograms/kg) were administered posttrial intraperitoneally (IP). Three inhibitory one-trial avoidance tasks were used; uphill, step-down and step-through (alcove). Habituation was measured in an open field by recording the number of rearings. The posttrial injection of SP facilitated avoidance responses as well as reduced rearing in a dose- and time-dependent way. Pretraining and pretest injections (IP) of naloxone facilitated avoidance behavior and potentiated the action of SP, also in a dose-dependent manner. These results demonstrate that: a) peripheral posttraining administration of SP enhances memory; b) SP facilitates not only aversive or positively motivated learning tasks, but also habituation, which is a form of learning that involves neither positive nor negative reinforces; c) SP does not exert its effect by a long-lasting proactive action on performance during the testing trial; d) naloxone potentiates the SP posttraining effect. These data, therefore, suggest that memory-enhancing effects of SP are, at least in part, mediated via interactions between this peptide and endogenous opioid systems.