ANXIOLYTIC-LIKE ACTION OF NEUROKININ SUBSTANCE-P ADMINISTERED SYSTEMICALLY OR INTO THE NUCLEUS BASALIS MAGNOCELLULARIS REGION

There is evidence that the neurokinin substance P plays a role in neur al mechanisms governing learning and reinforcement. Reinforcing and me mory-promoting effects of substance P were found after it was injected into several parts of the brain and intraperitoneally. With regard to the close Link between anxiety and memory processes for negative rein forcement learning, the aim of the present study was to gauge the effe ct of substance P on anxiety-related behaviors in the rat elevated plu s-maze and social interaction test. Substance P was tested at injectio n sites where the neurokinin has been shown to promote learning and to serve as a reinforcer, namely in the periphery (after i.p. administra tion) and after injection into the nucleus basalis magnocellularis reg ion. When administered i.p., substance P had a biphasic dose-response effect on behavior in the plus-maze with an anxiolytic-like action at 50 mu g/kg and an anxiogenic-like one at 500 mu g/kg. After unilateral microinjection into the nucleus basalis magnocellularis region, subst ance P (1 ng) was found to exert anxiolytic-like effects, because subs tance P-treated rats spent more time on the open arms of the plus-maze and showed an increase in time spent in social interaction. Furthermo re, the anxiolytic effects of intrabasalis substance P were sequence-s pecific since injection of a compound with the inverse amino acid sequ ence of substance P (0.1 to 100 ng) did not influence anxiety paramete rs. These results show that substance P has anxiolytic-like properties in addition to its known promnestic and reinforcing effects, supporti ng the hypothesis of a close relationship between anxiety, memory and reinforcement processes. (C) 1998 Elsevier Science B.V. All rights res erved.