CORTICOTROPIN-RELEASING FACTOR NEUROTRANSMISSION IN LOCUS-COERULEUS -A POSSIBLE SITE OF ANTIDEPRESSANT ACTION

Hypersecretion of corticotropin-releasing factor (CRF), has been hypot hesized to occur in depression. Because CRF may serve as a neurotransm itter in the locus coeruleus (LC), it was proposed that CRF hypersecre tion in the LC is responsible for some characteristics of depression, and that antidepressants act by interfering with CRF neurotransmission in the LC. To test this hypothesis, the acute and chronic effects of four antidepressants and cocaine were characterized on LC spontaneous and sensory-evoked discharge, LC activation by a stressor that require s CRF release, and LC activation by exogenously administered CRF. None of the antidepressants or cocaine altered LC activation by intracereb roventricularly administered CRF (3.0 mu g) after chronic administrati on. However, chronic administration of desmethylimipramine and mianser in inhibited LC activation by a hypotensive stress that requires endog enous CRF release, suggesting that they decrease CRF release in the LC . Chronic administration of sertraline and phenelzine altered LC respo nses to repeated sciatic nerve stimulation in a manner opposite to the effect produced by CRF, suggesting that these drugs may functionally antagonize CRF actions in the LC. Cocaine did not appear to interfere with CRF actions in the LC. In conclusion, chronic administration of a ntidepressants may have the potential to interfere with CRF neurotrans mission in the LC.