Ultrastructural localization of the CB1 cannabinoid receptor in μ-opioid receptor patches of the rat caudate putamen nucleus

Cannabinoids and opioids are widely consumed drugs of abuse that produce motor depression, in part via respective activation of the cannabinoid subtype 1 receptor (CB1R) and the mu -opioid receptor (mu OR), in the striatal circuitry originating in the caudate putamen nucleus (CPN). Thus, the CB1R and mu OR may show similar targeting in the CPN. To test this hypothesis, we examined the electron microscopic immunocytochemical labeling of CB1R and mu OR in CPN patches of rat brain. Of the CB1R-labeled profiles, 34% (588) were dendrites, presumably arising from spiny as well as aspiny-type somata, which also contained CB1R immunoreactivity. In dendrites, CB1R often was localized to nonsynaptic and synaptic plasma membranes, particularly near asymmetric excitatory-type junctions. Almost one-half of the CB1R-labeled dendrites contained mu OR immunoreactivity, whereas only 20% of all mu OR-labeled dendrites expressed CB1R. Axons and axon terminals as well as abundant glial processes also showed plasmalemmal CB1R and were mainly without mu OR immunoreactivity. Many CB1R-labeled axon terminals were small and without recognizable synaptic junctions, but a few also formed asymmetric, or more rarely symmetric, synapses. The CB1R-labeled glial processes were often perivascular or perisynaptic, surrounding asymmetric excitatory-type axospinous synapses. Our results show that in CPN patches CB1R and mu OR are targeted strategically to some of the same postsynaptic neurons, which may account for certain similarities in motor function. Furthermore, they also provide evidence that CB1R may play a major role in the modulation of presynaptic transmitter release and glial functions that are unaffected in large part by opioids active at mu OR in CPN.