EXPRESSION OF MU-OPIOID RECEPTOR MESSENGER-RNA IN RAT-BRAIN - AN IN-SITU HYBRIDIZATION STUDY AT THE SINGLE-CELL LEVEL

The mu (CL) opioid receptors, which mediate the effects of morphine, a re widely distributed in brain. We have examined the distribution of m RNA encoding a mu opioid receptor in rat brain with in situ hybridizat ion histochemistry at the single-cell level to obtain information abou t the cell types synthesizing this receptor. Only neurons, not glia, w ere labeled in discrete brain regions. High levels of labeling were de tected in the thalamus, striosomes of the caudate-putamen, globus pall idus, and brain regions involved in nociception, arousal, respiratory control, and, possibly, addiction. The general distribution of the rec eptor mRNA paralleled that of mu opioid binding sites with some notabl e exceptions. These include the cerebral cortex, which contains bindin g sites, but very few labeled neurons. No labeling was observed in the cerebellum, a region devoid of mu binding sites. Three main findings emerged from these experiments: 1) the mRNA was present in regions med iating both the therapeutic (analgesia) and the unwanted (respiratory depression, addiction) effects of morphine, 2) the mRNA was very dense ly expressed by neurons known to receive dense enkephalin-containing i nputs, and 3) the dissociation between the presence of binding sites a nd absence of mRNA in some brain regions supports a presynaptic locali zation of mu opioid receptors in these areas. Alternatively, other sub types of mu opioid receptors may be encoded by a different mRNA. These results provide new insights into the receptor types and neuronal cir cuits involved in the effects of endogenous opioids and morphine. (C) 1994 Wiley-Liss, Inc.