AVERSIVE EFFECTS OF THE C-FRAGMENT OF SUBSTANCE-P IN THE DORSAL PERIAQUEDUCTAL GRAY-MATTER

There has been an increasing interest in the role of neuropeptides in the integration of brain functions. Besides the well-known positive-re inforcing effects of Substance P (SP) in prosencephalic regions, a rol e of this neuropeptide in the generation of aversive states in mesence phalic structures has also been envisaged. Evidence from a previous st udy suggests an involvement of SP in the neural substrates of aversion in the dorsal periaqueductal gray matter (DPAG). Tn the present study , we investigate whether N- and C-terminal fragments of Substance P ar e responsible for the effects produced by microinjections of SP into t he dorsal periaqueductal gray. The results show that SP and its C-term inal fragment SP7-11 produced a behavioral activation with increases i n locomotor activity, grooming, and rearings, while the N-terminal fra gment S1-7 produced only an increase in vertical exploratory activity. The effects were more pronounced with intermediate doses of SP and it s C-fragment, confirming the characteristic bell-shaped dose-effect fu nction of this neuropeptide. The proaversive effects observed with DPA G microinjections of these neuropeptides in the present study gain fur ther relevance when combined with previous reports showing uncondition ed and conditioned aversive effects following DPAG microinjections of SP in the place aversion and the elevated plus maze tests, two widely used animal models of anxiety. These results confirm previous data sho wing that SP has a modulatory role in the DPAG and that its effects ar e probably due to its C-terminal fragment.