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Acute Effects of Cholecystokinin Tetrapeptide on Brain Stem Auditory Evoked Potentials in Healthy Volunteers
Linköping University, Department of Neuroscience and Locomotion, Psychiatry. Linköping University, Faculty of Health Sciences.
Royal Ottawa Hospital, Ottawa, Ontario, Canada.
Department of Psychiatry, University of Tartu, Estonia.
Department of Psychiatry, University of Ottawa/Royal Ottawa Hospital and Institute of Mental Health Research, Ottawa, Ontario, Canada.
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2003 (English)In: Pharmacopsychiatry, ISSN 0176-3679, E-ISSN 1439-0795, Vol. 36, no 5, 181-186 p.Article in journal (Refereed) Published
Abstract [en]

This study investigated the effects of continuous slow intravenous infusion of cholecystokinin tetrapeptide (CCK-4) on brain stem auditory evoked potentials (BSAEP) in healthy subjects. Twenty-four subjects, 15 females and 9males, were assigned to infusion with either placebo or CCK-4 in a randomized, double-blind, parallel group design. BSAEPs, mood, physical symptoms, and vital signs were assessed once before infusion and at 10 min and 40 min after the onset of infusion. In the 16 subjects (N = 8, CCK-4; N = 8, placebo) CCK-4, compared to placebo, delayed peak I latency during early infusion, slowed the latencies of peaks III and V, and decreased the amplitude of peak III throughout the infusion. No significant treatment differences were observed with respect to symptoms, mood, or cardiovascular measures. These preliminary findings suggest that CCK-4 may interfere with information processing in the brain stem auditory pathways and that prolonged intravenous CCK-4 administration may be a useful challenge paradigm for investigating CCK's modulatory role on brain stem mechanisms mediating anxiety and panic in humans.

Place, publisher, year, edition, pages
2003. Vol. 36, no 5, 181-186 p.
Keyword [en]
Cholecystokinin, CCK-4, brain stem auditory evoked potentials, anxiety, panic
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-27796DOI: 10.1055/s-2003-43047Local ID: 12543OAI: oai:DiVA.org:liu-27796DiVA: diva2:248348
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
In thesis
1. On the cerebrospinal fluid disposition and neurobiological role of cholecystokinin in man
Open this publication in new window or tab >>On the cerebrospinal fluid disposition and neurobiological role of cholecystokinin in man
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cholecystokinin (CCK) is the most abundant neuropeptide in the brain, where it acts as a neurotransmitter and neuromodulator. The tetrapeptide CCK-4 and the octapeptide CCK-8 have been implicated in various behavioural and physiological functions, such as anxiety, pain and satiety. Analyses of the levels of CCK in plasma, CSF and brain tissue have been used in studies aimed at elucidating the pathophysiological mechanisms in psychiatric disorders, but the results have been inconsistent.

Cerebrospinal fluid (CSF) levels of CCK-4 and CCK-8S were analysed in three groups of healthy subjects lumbar-punctured under different conditions, with the aim to provide reference values for studies on patients, and to investigate putative confounding factors. It was found that the concentrations of CCK-4 and CCK-8S were influenced by age, bedrest or not prior to lumbar puncture, neuraxis distance, position during lumbar puncture, height, atmospheric pressure and storage time. For a correct interpretation of data, these factors should be taken into account in future CSF studies in volunteers and patients.

Hypothyroidism is associated with depression. Thyroid hormones have been assumed to affect neuronal functions in the CNS, and animal experiments have indicated a relationship between thyroid hormones and CCK. Depressive symptoms were assessed in hypothyroid patients who were also lumbar-punctured before and during L-thyroxine treatment. Thyroid stimulating hormone, tri-iodothyronine and thyroxine in serum correlated with both CCK peptides in the CSF. A negative correlation between CCK-4 and inner tension (anxiety) was found.

Various studies implicate the involvement of brain-stem structures in the aetiology of panic attacks. Brain-stem auditory evoked potentials were recorded in healthy subjects before and during infusion with the panic-provoking agent CCK-4 or placebo. CCK-4 delayed the latencies of peak I, III and V, and decreased peak III amplitude. This suggests that exogenous CCK-4 affects stimulus processing in the brain stem.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 70 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 643
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28039 (URN)12800 (Local ID)91-7219-744-7 (ISBN)12800 (Archive number)12800 (OAI)
Public defence
2000-10-20, Berzeliussalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-14Bibliographically approved

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