Repetitive intranasal administration of cholecystokinin potentiates its central nervous effects

• Published in: Physiology & behavior 2004-10, Vol.83 (1), p.39-45
• Main Authors: Denecke, Heide, Meyer, Frank, Feldkamp, Joachim, Fritzen, Reimar, Pietrowsky, Reinhard
• Format: Article
• Language: English
• Subjects: Cholecystokinin; ERP; Event-related brain potentials; Humans; Nose–brain pathway; P300; Slow-wave
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2004.07.021

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-μg 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.