Time Course of Intranasally Administered Cholecystokinin-8 on Central Nervous Effects

Abstract

The gut and brain peptide cholecystokinin (CCK) exerts a number of central nervous effects. Among them are effects on attention and stimulus processing as revealed by modulations of event-related potentials (ERPs). In the present study the time course of central nervous effects after an intranasal administration of CCK-8 was investigated by means of ERPs. ERPs were recorded in an oddball paradigm 15, 30, 60, 90, 120, and 240 min after administration. Following the double-blind intranasal administration of CCK-8 and placebo, the late positive complex (LPC) of the ERP was significantly increased following CCK-8 compared to placebo. This effect was more pronounced in women than in men. The enhancement of the LPC by intranasal CCK-8 was not restricted to a specific recording time but reached its maximum 120 min after administration in men and women. Moreover, results tentatively indicate that 30 min after administration of CCK-8 the LPC increased only in women but not in men. The early effect of intranasal CCK-8 on LPC in women is unlikely to be caused by changes in plasma CCK-8 levels and suggests a direct nose-brain pathway.

Is nose-to-brain transport of drugs in man a reality?

“…Similar results were obtained by the same group after nasal and intravenous administration of cholecystokinin-8 (Pietrowsky et al 1996b) and performance of an auditory attention task (oddball task) in 20 volunteers in a double blind cross-over study recording the auditory event-related brain potentials. Further studies confirmed the results (Pietrowsky et al 2001).…”

Intranasal administration of oxytocin: Behavioral and clinical effects, a review

“…From these data, two 'general rules' emerge: after IN-administration: (1) brain/CSF-levels tend to be higher than the peripheral levels, sometimes higher than the levels obtained after i.v.-administration; (2) peripheral levels rise more slowly and are generally preceded by steeper rising brain/CSF-levels. Such effects have been shown for neuropeptides and hormones like CCK-8 (Pietrowsky et al, 2001(Pietrowsky et al, , 1996, vascular endothelial growth factor (VEGF) , MSH/ACTH (Born et al, 2002), insulin-like growth factor-1 (Thorne et al, 2004) and hexarelin (Yu and Kim, 2009), as well as for a variety of other substances like testosterone (Banks et al, 2009), estradiol (Ohman et al, 1980;Wang et al, 2006), ergoloid mesylate , gastrodin (Wang et al, 2007, cephalexin (Sakane et al, 1991), tetramethylpyrazine (Feng et al, 2009), and the angiotensin antagonist GR138950 (Charlton et al, 2008). This list can be extended easily but these suffice to illustrate that INadministration of substances mostly results in faster peaks and/or higher brain concentrations than peripheral administration.…”

“…Occasionally, in human studies, the behavioral effects of IN-OT were studied after about an hour (Burri et al, 2008). However, plasma levels of OT were elevated already within 20 min (Burri et al, 2008;Landgraf, 1985), whereas the central nervous effects of a neuropeptide of similar size (cholecystokinin, CCK-8, MW 1143) were most clearly obtained at 15-30 min after IN-administration (Pietrowsky et al, 2001). The finding that plasma OT-levels remain elevated for a long time (more than 80 min!)…”

Brain potential signs of slowed stimulus processing following cholecystokinin in Parkinson's disease

“…AEPs were measured 45 min after substance administration while the subjects performed an oddball task in a sound-attenuated and electrically shielded room. The time of drug administration was chosen based on foregoing results in healthy subjects although more recent data indicate that a more delayed AEP recording would have been preferable (Pietrowsky et al 1996b(Pietrowsky et al , 2001. The task stimuli were 200 tone pips (60 ms duration) binaurally presented via headphones (beyerdynamic DT48, 800 Ω, Germany) at an intensity of 60 dB SPL.…”