Expression of Mu opioid receptor mRNA in rat brain: An in situ hybridization study at the single cell level

Abstract

The mu (mu) opioid receptors, which mediate the effects of morphine, are widely distributed in brain. We have examined the distribution of mRNA encoding a mu opioid receptor in rat brain with in situ hybridization histochemistry at the single-cell level to obtain information about the cell types synthesizing this receptor. Only neurons, not glia, were labeled in discrete brain regions. High levels of labeling were detected in the thalamus, striosomes of the caudate-putamen, globus pallidus, and brain regions involved in nociception, arousal, respiratory control, and, possibly, addiction. The general distribution of the receptor mRNA paralleled that of mu opioid binding sites with some notable exceptions. These include the cerebral cortex, which contains binding 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 mediating both the therapeutic (analgesia) and the unwanted (respiratory depression, addiction) effects of morphine, 2) the mRNA was very densely expressed by neurons known to receive dense enkephalin-containing inputs, and 3) the dissociation between the presence of binding sites and absence of mRNA in some brain regions supports a presynaptic localization of mu opioid receptors in these areas. Alternatively, other subtypes of mu opioid receptors may be encoded by a different mRNA. These results provide new insights into the receptor types and neuronal circuits involved in the effects of endogenous opioids and morphine.

Prolonged Effects of Repeated Social Defeat Stress on mRNA Expression and Function of μ-Opioid Receptors in the Ventral Tegmental Area of Rats

“…Analysis of film autoradiograph revealed that m-opioid receptor mRNA exhibited low constitutive expression in the VTA of control rats, in agreement with previously described low basal m-opioid receptor mRNA expression in rat VTA (Mansour et al, 1994;Delfs et al, 1994). The autoradigraphic density of m-opioid receptor mRNA labeling significantly increased after repeated social defeat stress.…”

Epileptiform synchronization in the rat insular and perirhinal cortices in vitro

“…Though the exact mechanism is unknown, IC outputs chronically regulate detection thresholds for painful stimuli in the periphery via GABAergic signais (Jasmin et al, 2003;Jasmin et aL, 2004). In addition, an unusually dense staining region for ~-opioid receptors (primary receptor targets for analgesia-producing opiates such as morphine) is present in the rostral agranular region (Delfs et aL, 1994;Burkey et aL, 1996). Of interest here, the IC is connected with other structures involved in TLE, such as the anterior hippocampus, the PC and the amygdala.…”

“…4AP application results in downregulation of the KCC2 co-transporter in hippocampal slices, resulting in intracellular CI-accumulation and hence depolarizing postsynaptic responses to GABA (Rivera et aL, 2004). It is thus possible that these potentials were not completely abolished despite the presence of DAGO due to strong somatic excitation mediated by interneuron recurrent collateral release of depolarizing GABA, to lead to large synchronized interneuronal network discharges (Michelson and Wong, 1994 (Delfs et aL, 1994;Burkey et aL, 1996;Jasmin et aL, 2003). The increased abundance of IJ-opioid receptors within the IC therefore may account for differences in response to DAGO between the PC and the IC, however more experimentation would be necessary to determine precisely how these phenomena relate.…”

Absence of Δ-9-Tetrahydrocannabinol Dysphoric Effects in Dynorphin-Deficient Mice

“…Conversely, THC withdrawal symptoms were significantly reduced in enkephalin-deficient animals . The expression of opioid and cannabinoid receptors overlaps in many brain areas, including structures of the reward circuitry (Herkenham, 1992;Matsuda et al, 1993;Delfs et al, 1994;Mansour et al, 1995a,b). Although colocalization studies with cellular resolution have not been performed yet, it has been suggested that both receptor types may interact at the level of signal transduction .…”