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Stress‐ and Yohimbine‐Induced Release of Cholecystokinin in the Frontal Cortex of the Freely Moving Rat: Prevention by Diazepam but Not Ondansetron
Author(s) -
Nevo Igal,
Becker Christel,
Hamon Michel,
Benoliel JeanJacques
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66052041.x
Subject(s) - microdialysis , yohimbine , chemistry , diazepam , endocrinology , cholecystokinin , medicine , pharmacology , raphe nuclei , bicuculline , anxiogenic , serotonin , anxiolytic , antagonist , dopamine , serotonergic , biochemistry , receptor
The in vivo release of cholecystokinin (CCK)‐like material (CCKLM) was measured in the frontal cortex of freely moving rats using the microdialysis technique combined with a sensitive radioimmunoassay. Local perfusion of K + (100 m M )‐enriched artificial CSF resulted in a 10‐fold increase in CCKLM outflow, as compared with that occurring under basal resting (K + = 3.0 m M ) conditions, and this effect could be completely prevented by removal of Ca 2+ in the perfusing fluid. Chromatographic analyses demonstrated that CCK‐8S contributed to 70% of CCKLM. Stressful stimuli such as a 2‐min exposure to diethyl ether and a 30‐min restraint produced a marked but transient increase in cortical CCKLM release. In addition, anxiety‐like behavior induced by the systemic administration of yohimbine (5 mg/kg i.p.) was associated with a long‐lasting enhancement in the peptide outflow. Pretreatment with the potent anxiolytic drug diazepam (5 mg/kg i.p., 5 min before each condition), which exerted no effect on its own, completely prevented CCKLM overflow due to diethyl ether, restraint, or yohimbine administration. In contrast, neither the systemic injection (0.1 mg/kg i.p.) nor the local application (100 µ M through the microdialysis probe) of the serotonin 5‐HT 3 antagonist ondansetron affected the increased release of CCKLM in rats restrained for 30 min or treated with yohimbine. These results indicate that cortical CCKergic neurotransmission is increased during stress or anxiety‐like behavior in rats. Prevention of this effect by diazepam suggests that an inhibitory influence of benzodiazepines on cortical CCKergic neurons might participate in the anxiolytic action of these drugs.