Stress-induced norepinephrine release in the rat prefrontal cortex measured by microdialysis

Norepinephrine (NE) release in the medial prefrontal cortex (PFC) of rats was studied during immobilization using an intracerebral microdialysis technique. A series of experiments using pharmacological and physiological manipulations indicated that the NE recovered in the medial PFC dialysate was mainly derived from nerve terminals and that the dorsal noradrenergic bundle was a major source of NE in the medial PFC. Immobilization stress immediately elevated NE levels to 176.0 +/- 9.0% of basal release, and this increase continued for the entire period of stress and 20 min after termination of the stress. Preinjection of a benzodiazepine receptor agonist, diazepam (5 mg/kg ip), significantly attenuated immobilization-induced NE release, while injection of an anxiogenic compound, FG-7142 (20 mg/kg ip), facilitated NE release in an obviously nonstressed condition. These results therefore suggest that stressful stimuli activate the NE system in the medial PFC, which may be modulated by an activation of benzodiazepine receptors in the brain.