Anxiolytic-like effects in rats produced by ventral pallidal injection of both N- and C-terminal fragments of substance P.
Prior studies have shown that the neurokinin substance P (SP) has anxiolytic-like effects when administered into the nucleus basalis (NB) area of the rat ventral pallidum. The present work was performed to examine whether the anxiolytic effects of SP in the nucleus basalis can be assigned its amino (N)- or carboxy (C)-terminal moiety. Using the elevated plus-maze model of anxiety in combination with unilateral injection of N-terminal SP(1-7) or C-terminal SP(7-11) into the NB region, we found that the treatment with either SP-fragment increased the number of entries into and time spent on the open arms as well as excursions into the end of the open arms, indicative of an anxiolytic-like profile. Furthermore, the effective doses of SP(1-7) (0.67 ng) and SP(7-11) (0.45 ng) were equimolar to the dosage of the whole SP molecule (1 ng), which was effective to reduce anxiety. Thus, the results support earlier findings that ventral pallidal injection of SP has anxiolytic-like effects and provide new evidence that fragments of SP, representing the N- and C-terminal domain of the peptide can reduce fear-parameters at a concentration similar to that of the parent peptide.
Nikolaus
S
S
Institute of Physiological Psychology & Center for Biological and Medical Research, University of Düsseldorf, Universitätsstrasse 1, D-40225, Düsseldorf, Germany.
Huston
J P
JP
Hasenöhrl
R U
RU
D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy; D020532:Basal Nucleus of Meynert / Q000187:drug effects* / Q000378:metabolism*; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D013373:Substance P