Repetitive intranasal administration of cholecystokinin potentiates its central nervous effects.
Functional evidence exists for a nose-brain pathway for the neuropeptide cholecystokinin-8 (CCK-8S). The transport mechanism, however, remains still unclear. Previous studies indicate a saturable dose-response curve on the magnitude of the late positive complex of the auditory event-related potential (AERP) with increasing doses of intranasally administered CCK-8S. Thus, the present study served to bypass this saturation by repeated lower dose intranasal administrations of CCK-8S. It was expected that this repetitive administration results in a nonsaturable dose-response effect on AERPs. AERPs reflecting cortical stimulus processing were recorded while subjects performed on an auditory attention task (oddball paradigm) four times (in intervals of 30 min) each following a separate 10-microg intranasal administration of CCK-8S or placebo. Compared with placebo, the repetitive intranasal administration of CCK-8S linearly enhanced the late positive complex and its subcomponent slow wave. Blood plasma CCK-8S levels were not affected by intranasal CCK-8S. The results suggest that by using a repetitive intranasal administration of CCK-8S, a saturable mechanism for central nervous CCK-8S effects can be avoided.
Denecke
Heide
H
Clinical Psychology, Heinrich-Heine-University Duesseldorf, Universitaetsstrasse 1, 40225 Duesseldorf, Germany.
Meyer
Frank
F
Feldkamp
Joachim
J
Fritzen
Reimar
R
Pietrowsky
Reinhard
R
D000161:Acoustic Stimulation; D000281:Administration, Intranasal; D000328:Adult; D019540:Area Under Curve; D001288:Attention / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D002766:Cholecystokinin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D002766:Cholecystokinin; D006854:Hydrocortisone