Intermittent and chronic morphine treatment induces long-lasting changes in δ-opioid receptor-regulated acetylcholine release in rat striatum and nucleus accumbens

1995 ◽  
Vol 283 (1-3) ◽  
pp. 169-176 ◽  
Author(s):  
Guno H.K. Tjon ◽  
Taco J. De Vries ◽  
Patrizia Nestby ◽  
George Wardeh ◽  
Arie H. Mulder ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Opioid Receptor ◽  
Acetylcholine Release ◽  
Rat Striatum ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Chronic Morphine Treatment ◽  
Δ Opioid Receptor

Increase in Adenosine Sensitivity in the Nucleus Accumbens Following Chronic Morphine Treatment

2002 ◽  
Vol 87 (3) ◽  
pp. 1369-1375 ◽  
Author(s):  
James M. Brundege ◽  
John T. Williams
Keyword(s):  
Nucleus Accumbens ◽  
Drug Addiction ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Adenosine Receptor Agonist ◽  
Adenosine Transport ◽  
Chronic Morphine Treatment

There is a growing body of evidence suggesting that the neuromodulator adenosine is involved in drug addiction and withdrawal and that adenosine signaling pathways may offer new targets for therapeutic treatments of addiction. Recent studies have suggested that chronic exposure to drugs of abuse may alter adenosine metabolism in the nucleus accumbens, a brain region critically involved in drug addiction and withdrawal. The present study examined the effects of chronic morphine treatment on the ability of adenosine to inhibit excitatory postsynaptic currents in nucleus accumbens medium spiny neurons. It was found that chronic morphine treatment via subcutaneous implantation of morphine pellets in rats for 1 wk did not alter the level of adenosine-mediated tonic inhibition of nucleus accumbens excitatory synapses. However, chronic morphine treatment did induce a leftward shift in the adenosine dose-response curve, indicating an increase in the sensitivity of synaptic currents to exogenously applied adenosine. This shift was not due to a change in adenosine receptors or their effectors, because chronic morphine treatment had no effect on the dose-response relationship of a nonmetabolized adenosine receptor agonist. When adenosine transport was blocked, the ability of chronic morphine to shift the adenosine dose-response curve was eliminated. These experiments suggest that the increase in the sensitivity of nucleus accumbens synapses to the inhibitory effects of adenosine may be due to a decrease in adenosine transport. The identification of these changes in the adenosine system after chronic drug exposure may help identify new therapeutic strategies aimed at easing withdrawal from opioids.

scholarly journals Chronic Morphine Treatment Alters NMDA Receptor-Mediated Synaptic Transmission in the Nucleus Accumbens

1999 ◽  
Vol 19 (20) ◽  
pp. 9081-9089 ◽  
Author(s):  
Gilles Martin ◽  
Serge H. Ahmed ◽  
Thomas Blank ◽  
Joachim Spiess ◽  
George F. Koob ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Nmda Receptor ◽  
Synaptic Transmission ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Chronic Morphine Treatment

Opioid receptor-coupled G-proteins in rat locus coeruleus membranes: decrease in activity after chronic morphine treatment

1997 ◽  
Vol 746 (1-2) ◽  
pp. 10-18 ◽  
Author(s):  
Dana E Selley ◽  
Eric J Nestler ◽  
Christopher S Breivogel ◽  
Steven R Childers
Keyword(s):  
Locus Coeruleus ◽  
G Proteins ◽  
Opioid Receptor ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Chronic Morphine Treatment

scholarly journals Cellular tolerance at the µ-opioid receptor is phosphorylation dependent

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Seksiri Arttamangkul ◽  
Daniel A Heinz ◽  
James R Bunzow ◽  
Xianqiang Song ◽  
John T Williams
Keyword(s):  
Opioid Receptor ◽  
Potassium Conductance ◽  
Cellular Level ◽  
Wild Type ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
C Terminus ◽  
Chronic Morphine Treatment ◽  
Cellular Tolerance

Phosphorylation of the μ-opioid receptor (MOR) is known as a key step in desensitization and internalization but the role in the development of long-term tolerance at the cellular level is not known. Viral expression of wild type (exWT) and mutant MORs, where all phosphorylation sites on the C-terminus (Total Phosphorylation Deficient (TPD)) were mutated to alanine, were examined in locus coeruleus neurons in a MOR knockout rat. Both receptors activated potassium conductance similar to endogenous receptors in wild type animals. The exWT receptors, like endogenous receptors, acutely desensitized, internalized and, after chronic morphine treatment, displayed signs of tolerance. However, TPD receptors did not desensitize or internalize with agonist treatment. In addition the TPD receptors did not develop cellular tolerance following chronic morphine treatment. Thus C-terminal phosphorylation is necessary for the expression of acute desensitization, trafficking and one sign of long-term tolerance to morphine at the cellular level.

Chronic Morphine Treatment Alters N-Methyl-d-aspartate Receptors in Freshly Isolated Neurons from Nucleus Accumbens

2004 ◽  
Vol 311 (1) ◽  
pp. 265-273 ◽  
Author(s):  
Gilles Martin ◽  
Ana Guadaño-Ferraz ◽  
Beatriz Morte ◽  
Serge Ahmed ◽  
George F. Koob ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Isolated Neurons ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
Chronic Morphine Treatment

scholarly journals Cellular tolerance at the μ-opioid receptor is phosphorylation dependent

2018 ◽  
Author(s):  
Seksiri Arttamangkul ◽  
Daniel A Heinze ◽  
James R Bunzow ◽  
Xianqiang Song ◽  
John T Williams
Keyword(s):  
Opioid Receptor ◽  
Potassium Conductance ◽  
Wild Type ◽  
Morphine Treatment ◽  
Chronic Morphine ◽  
C Terminus ◽  
Μ Opioid Receptor ◽  
Chronic Morphine Treatment

AbstractThe role of phosphorylation of the μ-opioid receptor (MOR) in desensitization, internalization and long-term tolerance was examined in locus coeruleus (LC) neurons. Viral expression of wild type (exWT) and mutant MORs, where all phosphorylation sites on the C-terminus (Total Phosphorylation Deficient (TPD)) were mutated to alanine, were examined in a MOR knockout rat. Both expressed receptors acutely activate potassium conductance similar to endogenous receptors in wild type animals. The exWT receptors, like endogenous receptors, displayed signs of tolerance after chronic morphine treatment. There was however a loss of agonist-induced desensitization and internalization in experiments with the TPD receptors. In addition the development of tolerance was not observed in the TPD receptors following chronic morphine treatment. The results indicate a key role of C-terminal phosphorylation in the expression of acute desensitization, trafficking and long-term tolerance to morphine.

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