Dopamine afferent islands were observed in rodent caudate-putamen only during development, whereas patches with intense mu-opioid receptor (MOR) immunoreactivity were seen throughout the life. We performed direct comparison between MOR patches and dopamine islands in the caudate-putamen of rat pups, by double immunofluorescence labeling for MOR and tyrosine hydroxylase. MOR patches were include...

Spinophilin, a dendritic spine-enriched scaffold protein, modulates synaptic transmission via multiple functions mediated by distinct domains of the protein. Here, we show that spinophilin is a key modulator of opiate action. Knockout of the spinophilin gene causes reduced sensitivity to the analgesic effects of morphine and early development of tolerance but a higher degree of physical depende...

Sexually dimorphic nociception and opioid antinociception is very pervasive but poorly understood.We had demonstrated that spinal morphine antinociception in females, but not males, requires the concomitant activation of spinal μand κ-opioid receptors (MOR and KOR, respectively). This finding suggests an interrelationship between MOR and KOR in females that is not manifest in males. Here,we sho...

Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools. In the present study, we employed modified exosomes expressing the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface to deliver opioid rece...

The effects of morphine are mediated mainly through the mu opioid receptor (MOR). Expression of the MOR is up-regulated during neuronal differentiation in P19 embryonal carcinoma cells and epigenetic changes play an important role in MOR up-regulation. This study investigates the basis for differentiation-dependent alterations of MOR chromatin by studying the recruitment or dissociation of seve...

It has previously been shown that nitric oxide (NO) synthase is involved in the development of opioid tolerance. The aim of the present work was to study the effect of NO on μ-opioid receptor (MOR) desensitization. Furthermore, we explored the possible role of reactive oxygen species (ROS) in this effect. Single-unit extracellular and whole-cell patch-clamp recordings were performed on locus co...

BACKGROUND The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood. RESULTS The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intr...

The canonical two neuron model of opioid reward posits that mu opioid receptor (MOR) activation produces reward by disinhibiting midbrain ventral tegmental area (VTA) dopamine neurons through inhibition of local GABAergic interneurons. Although indirect evidence supports the neural circuit postulated by this model, its validity has been called into question by growing evidence for VTA neuronal ...

The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activ...

In December 2000, physicians in the Republic of the Marshall Islands reported the first known outbreak of Vibrio cholerae O1 infection (biotype El Tor, serotype Ogawa) from this country. In a matched case-control study on Ebeye Island, patients with cholera (n=53) had greater odds than persons without cholera (n=104) to have drunk adequately chlorinated water collected from a US military instal...