Neurokinin-1 receptor antagonism by SR140333: enhanced in vivo ACh in the hippocampus and promnestic post-trial effects.

Journal article

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.

Authors: Kart, E; Jocham, G; Müller, C; Schlömer, C; Brandão, M

• Journal: Peptides
• Volume: 25
• Issue: 11
• Pages: 1959-1969
• Publication date: 2004-11-01
• DOI: 10.1016/j.peptides.2004.07.003
• EISSN: 1873-5169
• ISSN: 0196-9781
• Language: English
• Keywords: Dose-Response Relationship, Drug; Behavior, Animal; Stereoisomerism; Amygdala; Injections, Intraperitoneal; Male; Rats; Quinuclidines; Receptors, Neurokinin-1; Memory; Rats, Wistar; Acetylcholine; Piperidines; Spatial Behavior; Avoidance Learning; Animals; Chromatography, High Pressure Liquid; Microdialysis; Hippocampus