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.
Becker
C
C
INSERM U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, Paris, France. becker@ext.jussieu.fr
Hamon
M
M
Benoliel
J J
JJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012149:Restraint, Physical; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013315:Stress, Psychological / Q000378:metabolism*; D013876:Thiophenes; D015016:Yohimbine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; D015016:Yohimbine; D002766:Cholecystokinin; C005632:tertatolol; D002065:Buspirone