Mechanisms of mu opioid receptor/G-protein desensitization in brain by chronic heroin administration

Maher, Catherine E.; Martin, Thomas J.; Childers, Steven R.

doi:10.1016/j.lfs.2005.03.004

Cited by 48 publications

(27 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The G/R ratio as we calculated should be interpreted with caution, because we did not determine B max of receptors or agonist-activated G proteins. Therefore, it is not equivalent to the amplification factor (Sim et al, 1996;Maher et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[³⁵S]Thiotriphosphate) Binding in the Guinea Pig

Wang

Rasakham²,

Huang³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

We examined whether sex differences in -opioid receptor (KOPR) pharmacology exist in guinea pigs, which are more similar to humans in the expression level and distribution of KOPR in the brain than rats and mice. The KOPR agonist trans-(Ϯ)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)benzeneacetamide methanesulfonate (U50,488H) produced a dose-dependent increase in abnormal postures and immobility with more effects in males than females. Males also showed more U50,488H-induced antinociception in the paw pressure test than females. Pretreatment with the KOPR antagonist norbinaltorphimine blocked U50,488H-induced abnormal body postures and antinociception. In contrast, inhibition of cocaine-induced hyperambulation by U50,488H was more effective in females than males. Thus, sex differences in the effects of U50,488H are endpoint-dependent. We then examined whether sex differences in KOPR levels and KOPR-mediated G protein activation in brain regions may contribute to the observed differences using quantitative in vitro autora-

show abstract

Section: Discussionmentioning

confidence: 99%

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[³⁵S]Thiotriphosphate) Binding in the Guinea Pig

Wang

Rasakham²,

Huang³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Therefore, changes in μOR expression or signal transduction pathways in the Acb may play key roles in the cellular plasticity induced by chronic opioid exposure. However, while μOR mRNA, protein, and ligand binding sites are enriched within the Acb (Mansour et al 1994;Moriwaki et al 1996), chronic morphine exposure does not appear to produce obvious signs of μOR plasticity in this brain region (Buzas et al 1996;Maher et al 2005;Noble and Cox 1996).…”

Section: Introductionmentioning

confidence: 90%

Chronic administration of morphine is associated with a decrease in surface AMPA GluR1 receptor subunit in dopamine D1 receptor expressing neurons in the shell and non-D1 receptor expressing neurons in the core of the rat nucleus accumbens

Glass

Lane

Colago

et al. 2008

Experimental Neurology

View full text Add to dashboard Cite

The nucleus accumbens (Acb) is an extensively studied neuroanatomical substrate of opiate reward and the neural plasticity associated with chronic opioid use. The cellular mechanisms mediating opioid-dependent plasticity are uncertain, however AMPA-type glutamate receptor trafficking in dopamine D1 dopamine receptor (D1R) expressing neurons may be a potential cellular pathway for these adaptations, although there is no evidence for this possibility. Immunogold electron microscopy was used to quantify the surface expression of the AMPA GluR1 subunit in dendritic profiles of neurons in the Acb in response to intermittent 14-day non-contingent injections of escalating doses of morphine, a model that parallels opioid self-administration. To determine if changes in GluR1 trafficking occurred in neurons potentially sensitive to dopamine-induced D1R activation, immunoperoxidase labeling of D1R was combined with immunogold labeling of GluR1.Immunogold quantification was performed in two distinct Acb subregions, the shell, an area involved in processing incentive salience related to rewarding stimuli, and the core, an area involved in rewardseeking behaviors. We provide the first report that chronic morphine administration is associated with a receptor-phenotypic decrease in surface trafficking of GluR1 in Acb subregions. When compared to saline injected animals, morphine produced a decrease in plasma membrane GluR1 labeling in medium-and large-size D1R expressing dendritic profiles in the Acb shell. In contrast, in the Acb core, surface GluR1 was decreased in small-size dendrites that did not express the dopamine receptor. These results indicate that chronic intermittent injection of escalating doses of morphine is accompanied by ultrastructural plasticity of GluR1 in neurons that are responsive to glutamate and dopamine-induced D1R activation in the Acb shell, and neurons capable of responding to glutamate but not D1R receptor stimulation in the Acb core. Thus, AMPA receptor trafficking associated with chronic opiate exposure in functionally distinct areas of the Acb may be distinguished by D1R receptor activation, suggesting the potential for differing neural substrates of reward and motor aspects of addictive processes involving glutamate and dopamine signaling.

show abstract

“…Wang and colleagues observed that DAMGO-induced MOR phosphorylation in the CPu was much lower than that in the thalamus [23]. Childers and colleagues reported that, after chronic heroin administration in rats, MOR desensitization was detected in some brain regions including thalamus and periaqueductal gray, but not in others including CPu and nucleus accumbens, as determined by DAMGO-stimulated [ 35 S]GTPγS binding [32]. Moreover, Noble and Cox found that MOR desensitization, defined as a reduced ability of agonists to inhibit adenylyl cyclase activity following chronic morphine treatment, occurred in thalamus and periaqueductal gray, but not in CPu and nucleus accumbens [33].…”

Section: Is N-glycosylation And/or Lipid Rafts Involved In Differentimentioning

confidence: 99%

Brain region-specific N-glycosylation and lipid rafts association of the rat mu opioid receptor

Huang

Chen

et al. 2008

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The mu opioid receptor (MOR) in the rat and mouse caudate putamen (CPu) and thalamus was demonstrated as diffuse and broad bands by western blot with polyclonal antibodies against a Cterminal peptide of MOR, which were absent in the cerebellum and brains of MOR-knockout mice. The electrophoretic mobility of MOR differed in the two brain regions with median relative molecular masses (Mr's) of 75 kDa (CPu) vs. 66 kDa (thalamus) for the rat, and 74 kDa (CPu) vs. 63 kDa (thalamus) for the mouse, which was due to its differential N-glycosylation. Rat MOR in CPu was found mainly associated with low-density cholesterol-and ganglioside M1 (GM1)-enriched fractions (lipid rafts), while the MOR in the thalamus was present in rafts and non-rafts without preference. Cholesterol reduction by methyl-β-cyclodextrin decreased DAGMO-induced [ 35 S]GTPγS binding in rat CPu membranes to a greater extent than in the thalamus membranes.

show abstract

Mechanisms of mu opioid receptor/G-protein desensitization in brain by chronic heroin administration

Cited by 48 publications

References 45 publications

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[³⁵S]Thiotriphosphate) Binding in the Guinea Pig

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[³⁵S]Thiotriphosphate) Binding in the Guinea Pig

Chronic administration of morphine is associated with a decrease in surface AMPA GluR1 receptor subunit in dopamine D1 receptor expressing neurons in the shell and non-D1 receptor expressing neurons in the core of the rat nucleus accumbens

Brain region-specific N-glycosylation and lipid rafts association of the rat mu opioid receptor

Contact Info

Product

Resources

About

Mechanisms of mu opioid receptor/G-protein desensitization in brain by chronic heroin administration

Cited by 48 publications

References 45 publications

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[35S]Thiotriphosphate) Binding in the Guinea Pig

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[35S]Thiotriphosphate) Binding in the Guinea Pig

Chronic administration of morphine is associated with a decrease in surface AMPA GluR1 receptor subunit in dopamine D1 receptor expressing neurons in the shell and non-D1 receptor expressing neurons in the core of the rat nucleus accumbens

Brain region-specific N-glycosylation and lipid rafts association of the rat mu opioid receptor

Contact Info

Product

Resources

About

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[³⁵S]Thiotriphosphate) Binding in the Guinea Pig

Sex Difference in κ-Opioid Receptor (KOPR)-Mediated Behaviors, Brain Region KOPR Level and KOPR-Mediated Guanosine 5′-O-(3-[³⁵S]Thiotriphosphate) Binding in the Guinea Pig