Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity

Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine... 213 112 112 2 3 J. P. Huston R. U. Hasenöhrl F. Boix P. Gerhardt R. K. W. Schwarting Institute of Physiological Psychology I Heinrich-Heine-University of Düsseldorf Universitätsstrasse 1 40225 Düsseldorf 1 Germany Abstract There is ample evidence that the neurokinin substance P (SP) can have neurotrophic as well as memory-promoting effects. This paper outlines a recent series of experiments dealing with the effects of SP and its N- and C-terminal fragments on memory, reinforcement, and brain monoamine metabolism. It was shown that SP, when applied peripherally (IP), promotes memory (inhibitory avoidance learning) and is reinforcing (place preference task) at the same dose of 37 nmol/kg. Most important, however, is the finding that these effects seemed to be encoded by different SP sequences, since the N-terminal SP1-7 (185 nmol/kg) enhanced memory, whereas C-terminal hepta- and hexapeptide sequences of SP proved to be reinforcing in a dose equimolar to SP. These differential behavioral effects were paralleled by selective and site-specific changes in dopamine (DA) activity, as both SP and its C-, but not N-terminus, increased extracellular DA in the nucleus accumbens (NAc), but not in the neostriatum. The neurochemical changes lasted at least 2 h after injection. These results show that the reinforcing action of peripheral administered SP may be mediated by its C-terminal sequence, and that this effect could be related to DA activity in the NAc. Direct application of SP (0.74 pmol) into the region of the nucleus basalis magnocellularis (NBM) was also memory-promoting and reinforcing, and again, these effects were differentially produced by the N-terminus and C-terminus, supporting the proposed structure-activity relationship for SP's effects on memory and reinforcement. These results may provide a hypothetical link between the memory-modulating and reinforcing effects of SP and the impairment in associative functioning accompanying certain neurodegenerative processes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity

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Publisher
Springer Journals
Copyright
Copyright © 1993 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
D.O.I.
10.1007/BF02244906
Publisher site
See Article on Publisher Site

Abstract

213 112 112 2 3 J. P. Huston R. U. Hasenöhrl F. Boix P. Gerhardt R. K. W. Schwarting Institute of Physiological Psychology I Heinrich-Heine-University of Düsseldorf Universitätsstrasse 1 40225 Düsseldorf 1 Germany Abstract There is ample evidence that the neurokinin substance P (SP) can have neurotrophic as well as memory-promoting effects. This paper outlines a recent series of experiments dealing with the effects of SP and its N- and C-terminal fragments on memory, reinforcement, and brain monoamine metabolism. It was shown that SP, when applied peripherally (IP), promotes memory (inhibitory avoidance learning) and is reinforcing (place preference task) at the same dose of 37 nmol/kg. Most important, however, is the finding that these effects seemed to be encoded by different SP sequences, since the N-terminal SP1-7 (185 nmol/kg) enhanced memory, whereas C-terminal hepta- and hexapeptide sequences of SP proved to be reinforcing in a dose equimolar to SP. These differential behavioral effects were paralleled by selective and site-specific changes in dopamine (DA) activity, as both SP and its C-, but not N-terminus, increased extracellular DA in the nucleus accumbens (NAc), but not in the neostriatum. The neurochemical changes lasted at least 2 h after injection. These results show that the reinforcing action of peripheral administered SP may be mediated by its C-terminal sequence, and that this effect could be related to DA activity in the NAc. Direct application of SP (0.74 pmol) into the region of the nucleus basalis magnocellularis (NBM) was also memory-promoting and reinforcing, and again, these effects were differentially produced by the N-terminus and C-terminus, supporting the proposed structure-activity relationship for SP's effects on memory and reinforcement. These results may provide a hypothetical link between the memory-modulating and reinforcing effects of SP and the impairment in associative functioning accompanying certain neurodegenerative processes.

Journal

PsychopharmacologySpringer Journals

Published: Sep 1, 1993

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