Stress- and yohimbine-induced release of cholecystokinin in the frontal cortex of the freely moving rat: prevention by diazepam but not ondansetron.

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 mM)-enriched artificial CSF resulted in a 10-fold increase in CCKLM outflow, as compared with that occurring under basal resting (K+ = 3.0 mM) conditions, and this effect could be completely prevented by removal of Ca2+ 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 microM through the microdialysis probe) of the serotonin 5-HT3 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.

[Effect of polarization of the frontal cortex on the resistance of the subcortical centers to ether]. / Vliianie poliarizatsii frontal'noi zony kory golovnogo mozga na ustoichivost' tsentrov podkorkovoi oblasti k éfiru.

Chronic experiments on unanesthetized rabbits have demonstrated that frontal cortex polarization with a constant anode current (5 mkA) elevates the resistance of bioelectrical activity to ether of the ipsilateral supervisual nucleus of the hypothalamus and midbrain reticular formation as well as the general endurance of the body. As compared with controls, the lifespan of experimental animals increases by 59.85 min, that is by 67.7% (P less than 0.01). In the awakening phase the restoration processes in bioelectrical activity of the cortex and subcortex centers of animals under polarization conditions are accelerated.

Leucine-enkephalin and methionine-enkephalin produce opposing effects on plasma corticosterone levels in ether-stressed mice.

The inhibitory effects of intracerebroventricular administration of saline on the plasma corticosterone response to ether stress in mice was reduced by Met-enkephalin and enhanced by Leu-enkephalin. When administered simultaneously the effects of the two peptides opposed each other. Met and Leu-enkephalin may subserve different physiological functions in the response of the hypothalamus-pituitary-adrenal system to stress.