Characterization of cannabinoid-1 receptors in the locus coeruleus: relationship with mu-opioid receptors.

The locus coeruleus (LC)-norepinephrine system is a target of both cannabinoid and opioid actions. The present study investigated the anatomical distribution of cannabinoid-1 receptor (CB1r) in the LC and its association with mu-opioid receptor (MOR). Immunoreactivity for CB1r was localized to pre- and postsynaptic cellular profiles in the LC, 82% of which were dual-labeled for tyrosine hydroxylase (TH). Of the CB1r-immunoreactive structures, 66% were somatodendritic profiles, 22% were axon terminals, and the remaining 12% were associated with glial and small unmyelinated axon-like structures. CB1r immunoreactivity (-ir) in somatodendritic profiles was more often localized to the cytoplasm, whereas CB1r-ir located in axon terminals was more commonly localized on the plasma membrane. Somatodendritic profiles with CB1r-ir typically received input from axon terminals forming asymmetric-type synapses. In contrast, presynaptic profiles with CB1r-ir typically formed symmetric synaptic specializations. Anatomical studies confirmed the co-existence of MOR and CB1r-ir in common somatodendritic compartments of catecholaminergic neurons in the LC, and also revealed CB1r-positive axon terminals forming synaptic contact with MOR-containing dendrites. Our results provide evidence for a heterogeneous distribution of CB1r in the LC and demonstrate that CB1r and MOR co-exist in cellular profiles in this region. These data suggest important potential interactions between cannabinoid and opioid systems in LC neuronal profiles that may impact noradrenergic tone. (c) 2009 Elsevier B.V. All rights reserved.