Dose response of arginine vasopressin to the CCK-B agonist pentagastrin

Cholecystokinin (CCK) is a peptide neurotransmitter that modulates hypothal mic-pituitary-adrenal (HPA) axis activity and may be involved in fear or an xiety states. Arginine vasopressin (AVP) also modulates HPA axis activity a nd may play a role in fear conditioning. Few human studies have examined in teractions between CCK and AVP systems. To explore relationships between CC K-B receptor activation, the HPA axis response, and AVP release, a dose-res ponse study using the CCK-B receptor agonist pentagastrin was conducted. Ad renocorticotropin (ACTH) and cortisol results have been previously reported and AVP data is presented here. Thirty-five healthy subjects were randomly assigned to receive placebo, or 0.2, 0.4, 0.6, or 0.8 mug/kg doses of pent agastrin. AVP release appeared to increase with increasing doses of the CCK -B agonist. However, this may have been due to a greater percentage of subj ects releasing AVP in the higher dose groups, rather than a direct effect o f dose on magnitude of response. AVP and ACTH responses were correlated, bu t AVP response alone could not account for the magnitude of the ACTH respon se. AVP release was significantly correlated with anxiety symptom responses . These findings suggest a possible role for the CCK-B receptor in AVP rele ase which may be at least partially separate from its role in modulation of the HPA axis. Further work is needed to determine whether these are physio logically meaningful interactions and to determine their functional implica tions. [Neuropsychopharmacology 24:161-169, 2001] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.