Ultrastructural evidence for co-localization of corticotropin-releasing factor receptor and μ-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 μ-opioid receptors (μORs) 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 μOR, immunofluorescence and electron microscopic analysis of the rat LC was conducted. Triple immunofluorescence showed prominent co-localization of the CRFr and μOR in noradrenergic somata in the LC. Ultrastructural analysis confirmed dual localization of CRFr and μOR in common dendritic processes in the LC. Semi-quantitative analysis showed that of the dendrites exhibiting CRFr immunolabeling, 57% expressed μOR immunoreactivity. These data provide ultrastructural evidence that CRFr and μOR are co-localized in LC neurons, a cellular substrate that may underlie opiate-induced sensitization of brain noradrenergic neurons to CRF.