Neurokinin-1 receptor antagonism by SR140333: enhanced in vivo ACh in the hippocampus and promnestic post-trial effects.
Substance P (SP) has memory-promoting, reinforcing and anxiolytic-like effects when applied systemically or centrally. Such effects may be mediated by the neurokinin-1 (NK-1) receptor, since SP preferentially binds to this receptor. We measured the effects of a selective non-peptide NK-1 receptor antagonist, SR140333 (1, 3 and 9 mg/kg i.p.) on ACh levels in frontal cortex, amygdala and hippocampus by microdialysis and HPLC. Levels of ACh in the hippocampus increased dose-dependently immediately after treatment. The same doses of SR140333 given post-trial had minor facilitative effects on inhibitory avoidance learning and open-field habituation, but did not have reinforcing effects in a conditioned place preference (CPP) task. The selective action of NK-1 receptor antagonism on hippocampal ACh may be related to its positive influence on learning.
Kart
Emriye
E
Institute of Physiological Psychology, Center for Biological and Medical Research, University of Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany. desouza@uni-desseldorf.de
Jocham
Gerhard
G
Müller
Christian P
CP
Schlömer
Cerstin
C
Brandão
Marcus L
ML
Huston
Joseph P
JP
de Souza Silva
M Angélica
MA
D000109:Acetylcholine / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D008568:Memory / Q000187:drug effects*; D017551:Microdialysis; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior; D013237:Stereoisomerism
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; C085215:SR 140333; D000109:Acetylcholine