CORTICOTROPIN-RELEASING FACTOR ADMINISTERED INTO THE LOCUS-COERULEUS,BUT NOT THE PARABRACHIAL NUCLEUS, STIMULATES NOREPINEPHRINE RELEASE IN THE PREFRONTAL CORTEX

Previous studies have indicated that intracerebroventricular applicati on of corticotropin-releasing factor (CRF) activates noradrenergic neu rons in the brain stem locus coeruleus (LC) and norepinephrine (NE) me tabolism in several brain regions. To assess whether CRF has direct ef fects on LC noradrenergic neurons, CRF was infused into the LC and con centrations of NE and its metabolites were measured in microdialysates collected from the medial prefrontal cortex (PFM). Infusion of 100 ng of CRF into the LC significantly increased dialysate concentrations o f NE and of its catabolite MHPG in the ipsilateral PFM, whereas no sig nificant changes were observed following infusion of artificial CSF. N o response was observed when the infusions of CRF occurred outside of the LC, including those in the parabrachial nucleus. Although CRF admi nistered into the LC slightly increased dialysate concentrations of NE in the contralateral PFM, this effect was not statistically significa nt. The effect of CRF injected into the LC on dialysate NE was prevent ed by combination with a 10-fold excess of the CRF antagonist, alpha-h elical CRF(9-41), indicating some specificity in the response. These r esults are consistent with anatomical and electrophysiological evidenc e suggesting that CRF may directly activate noradrenergic neurons in o r close to the LC.