CRF Receptor Antagonist Attenuates Immobilization Stress-Induced Norepinephrine Release in the Prefrontal Cortex in Rats

Neuroanatomical, neurophysiological, and behavioral studies suggest that brain stem nucleus locus coeruleus (LC) plays an important role in stress response. The present study was designed to clarify, whether infusion of CRF antagonist, αhCRF, into LC could attenuate or block stress-induced changes in norepinephrine (NE) concentrations in microdialysates collected from the medial prefrontal cortex (PFM). Rats were implanted with a bilateral cannulae assembly aimed in the LC and a microdialysis probe (4 mm active membrane length) into the LC. Immobilization of animals significantly increased the concentration of NE in microdialysates from PFM to a maximum of 170.8 ± 12.8% of the baseline ten minutes after the onset of stressor. Concentration of NE in dialysates remained significantly elevated for the next 40 min. Infusion of αhCRF into the LC significantly attenuated stress-induced increase in PFM NE concentration in samples collected at 10, 20, 30, and 50 min after the onset of immobilization. Infusion of αhCRF alone (no immobilization) did not change concentrations at any time during sample collection. These results are consistent with other studies and suggest that stress can facilitate NE release in the PFM through the activation of the CRF system in the brain.