Prevention by 5-HT1A receptor agonists of restraint stress- and yohimbine-induced release of cholecystokinin in the frontal cortex of the freely moving rat.

In line with the idea that cholecystokinin (CCK) is involved in anxiety-related behaviours, previous investigations showed that stressful conditions and an 'anxiogenic' drug, yohimbine, increased the cortical release of CCK like-material (CCKLM) in awake rats, and that this effect could be prevented by diazepam. Here, we investigated whether other anxiolytic drugs such as 5-HT1A receptor agonists could also affect cortical CCKLM release. Indeed, neither buspirone (1 mg/kg i.p.), alnespirone (1 mg/kg i.p.) nor lesopitron (3 mg/kg i.p.) affected, on their own, CCKLM release. However, pretreatment with the latter drugs completely abolished the stimulatory effect of restraint stress on the peptide outflow. As expected of the involvement of 5-HT1A receptors, tertatolol (10 mg/kg i.p) markedly reduced the inhibitory effect of buspirone on restraint stress-evoked CCKLM overflow. On the other hand, pretreatment with buspirone, alnespirone or lesopitron also inhibited the stimulatory effect of yohimbine (5 mg/kg i.p.) on cortical CCKLM outflow. These data support the idea that the anxiolytic action of 5-HT1A receptor agonists could be mediated, at least partly, through their inhibitory influence on cortical CCK-ergic systems.