Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat

Abstract

Adult male Sprague–Dawley rats were administered the 5-HT subtype selective receptor agonists 8-OH-DPAT (0.5–2.0mg/kg) (5-HT1B), buspirone (2–8mg/kg) (5-HT1A), TFMPP (0.125–2.0mg/kg), DOI (0.125–2.0mg/kg) (5-HT2A) and m-CPBG (1.25–20.0mg/kg) (5-HT3), subcutaneously. Oxytocin, cholecystokinin (CCK), somatostatin and gastrin plasma levels were determined by standard RIA techniques 30 and 120min after injection of the respective 5-HT receptor agonist. It was found that the 5-HT1A and the 5-HT2A/C, but not the 5-HT2B or the 5-HT3 receptor agonists produced an increase in plasma oxytocin levels and these effects were, at least partially, antagonized by the corresponding subtype selective antagonists (−)pindolol (2mg/kg) and ritanserin (2mg/kg), respectively, administered 10min before 8-OH-DPAT (0.5mg/kg) or DOI (0.5mg/kg). The maximal response to the 5-HT1A receptor agonists (approx. 120nmol/l) was from 8 to 5 times the maximal response to the 5-HT2A/C receptor agonist. In addition, 8-OH-DPAT and DOI caused a decrease in plasma CCK levels, whereas the 5-HT1B receptor agonist TFMPP gave rise to an increase in plasma CCK levels. There were no statistically significant effects by any of the 5-HT receptor agonists on plasma somatostatin or gastrin levels under the present conditions. It is suggested that the clinical effects of new anxiolytic 5-HT1A receptor agonists, such as buspirone, to an extent may be mediated via an increased release of oxytocin.