Ultrastructural evidence for co-localization of corticotropin-releasing factor receptor and mu-opioid receptor in the rat nucleus locus coeruleus.

Previous studies have shown that corticotropin-releasing factor (CRF), an integral mediator of the stress response, and opioids regulate the activity of the locus-coeruleus-norepinephrine (LC-NE) system during stress in a reciprocal manner. Furthermore, repeated opiate exposure sensitizes noradrenergic neurons to CRF. Previous studies have shown that mu-opioid receptors (muORs) are prominently distributed within somatodendritic processes of catecholaminergic neurons in the LC and axon terminals containing opioid peptides and CRF converge within the LC. To further examine cellular sites for interactions between CRF receptor type 1 (CRFr) and muOR, immunofluorescence and electron microscopic analysis of the rat LC was conducted. Triple immunofluorescence showed prominent co-localization of the CRFr and muOR in noradrenergic somata in the LC. Ultrastructural analysis confirmed dual localization of CRFr and muOR in common dendritic processes in the LC. Semi-quantitative analysis showed that of the dendrites exhibiting CRFr immunolabeling, 57% expressed muOR immunoreactivity. These data provide ultrastructural evidence that CRFr and muOR are co-localized in LC neurons, a cellular substrate that may underlie opiate-induced sensitization of brain noradrenergic neurons to CRF.