On the cerebrospinal fluid disposition and neurobiological role of cholecystokinin in man

Abstract: 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.