ACTIVATION OF NORADRENERGIC NEURONS IN THE LOCUS-COERULEUS BY CORTICOTROPIN-RELEASING FACTOR - A MICRODIALYSIS STUDY

In the present study the effects of different doses of corticotropin-r eleasing factor (CRF) and the CRF antagonist alpha-helical CRF on locu s coeruleus (LC) eurons were studied in anesthetized male Wistar rats. To monitor the release of noradrenaline (NA) and its metabolite 3-met hoxy-4-hydroxyphenylethylene glycol (MHPG), a microdialysis probe was implanted into the parietal cortex, a major projection area of the LC. Saline, 0.17, 0.51 nmol CRF and a combination of 5.1 nmol alpha-helic al CRF and 0.51 nmol CRF were applied to the LC via a fused silica cap illary. While both doses of CRF augmented NA in parietal cortex dialys ates (0.51 nmol CRF: from 0.0206 to 0.0266 pmol/sample, 0.17 nmol CRF: from 0.0147 to 0.0170 pmol/sample), saline did not affect NA concentr ation. The metabolite MHPG also increased, but in a more prolonged tim e course. The antagonist alpha-helical CRF attenuated the CRF effects. The increase of extraneuronal NA concentration monitored in the corti cal samples indicates an augmented depolarization rate of noradrenergi c LC neurons. This clearly demonstrates the activation of these neuron s by CRF, suggesting physiological interactions of CRF and noradrenerg ic neurons.