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-releasing factor (CRF) and the CRF antagonist alpha-helical CRF on locus coeruleus (LC) neurons were studied in anesthetized male Wistar rats. To monitor the release of noradrenaline (NA) and its metabolite 3-methoxy-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-helical CRF and 0.51 nmol CRF were applied to the LC via a fused silica capillary. While both doses of CRF augmented NA in parietal cortex dialysates (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 concentration. The metabolite MHPG also increased, but in a more prolonged time course. The antagonist alpha-helical CRF attenuated the CRF effects. The increase of extraneuronal NA concentration monitored in the cortical samples indicates an augmented depolarization rate of noradrenergic LC neurons. This clearly demonstrates the activation of these neurons by CRF, suggesting physiological interactions of CRF and noradrenergic neurons.