Quantitative light microscopic localization of [3H]naltrindole binding sites in the rat brain

Drower, Edward J.; Dorn, Clifford R.; Markos, Charles S.; Unnerstall, James R.; Rafferty, Michael; Contreras, Patricia C.

doi:10.1016/0006-8993(93)90253-j

Cited by 17 publications

(9 citation statements)

References 16 publications

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“…The regulation of mRNA levels is 1993). Furthermore, the relative abundance of DOR mRNA for each site also shows an excellent correspondence with the DOR binding and autoradiographic density previously described (Moskowitz and Goodman, 1984;Mansour et al, 1988;Drower et al, 1993;Mansour et al, 1993), suggesting that the antinociceptive effects of supraspinally administered DOR ligands probably occur, at least in part, at DOR receptors located within the regions we have surveyed. The ability to obtain quantitative data regarding the levels of DOR mRNA at selected brain loci makes solution hybridization an important tool in the study of receptor regulation.…”

Section: Discussionsupporting

confidence: 83%

Supraspinal delta opioid receptor mRNA levels are not altered in [D‐Ala²]Deltorphin II tolerant mice

Kest

Jenab

Brodsky

et al. 1994

J of Neuroscience Research

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Delta opioid receptor (DOR) mRNA levels were studied in mice rendered tolerant to [D-Ala2]deltorphin II by 4 days of repeated intracerebroventricular administration (10 micrograms, [tid]). ED50 determinations on day 5 revealed a 10-fold loss in [D-Ala2]deltorphin II potency with the tail-flick test. Utilization of a microdissection technique followed by quantitative solution hybridization of RNA extracts from mouse brain revealed mean levels of DOR mRNA ranging from 3.9 pg/micrograms RNA in the caudate-putamen to 0.4 pg/micrograms RNA in the cerebellum. DOR mRNA levels were not different when RNA extracts from tolerant and non-tolerant mice were compared. These data suggest that altered DOR mRNA levels are not one of the adaptive changes that occur with delta opioid ([D-Ala2]deltorphin II) tolerance.

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Section: Discussionsupporting

confidence: 83%

Supraspinal delta opioid receptor mRNA levels are not altered in [D‐Ala²]Deltorphin II tolerant mice

Kest

Jenab

Brodsky

et al. 1994

J of Neuroscience Research

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“…In rat striatal sections, delta opioid receptors showed a nonpatchy distribution in the striatum, with an increasing medial‐to‐lateral gradient. This is in agreement with previous reports 14, 35, 54. A high‐density binding was observed in the cerebral cortex and a low‐binding density was found in the globus pallidus.…”

Section: Discussionsupporting

confidence: 93%

“…However, previous studies on opioid radioligand binding have shown that dopamine denervating lesions33, 36 or chronic treatment with opioid agonists56 affect the B max and not K D values. The concentration of naltrindole used in the present study (0.3 nM) was equal to the K D of this radioligand as determined in a previously published receptor binding study 54. Thus, by using this nonsaturating concentration of radioligand, should any changes in either K D or B max have occurred, then they would have affected receptor binding.…”

Section: Discussionmentioning

confidence: 93%

Striatal delta opioid receptor binding in experimental models of Parkinson's disease and dyskinesia

Hallett

Brotchie

2007

Movement Disorders

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Enhanced delta opioid receptor transmission may represent an endogenous compensatory mechanism in parkinsonism to reduce the activity of the indirect striatopallidal pathway following dopamine depletion. Furthermore, increased delta opioid receptor transmission may be causative in the production of dyskinesia following repeated dopaminergic treatment in Parkinson's disease. The present study employed radioligand receptor autoradiography, using [3H]naltrindole, a ligand selective for the delta opioid receptor, to assess delta opioid receptor binding sites in forebrain regions of reserpine-treated rats, and in parkinsonian nondyskinetic, and dyskinetic MPTP-lesioned macaques. In reserpine-treated animals, specific delta opioid binding was increased in premotor cortex (+30%), sensorimotor striatum (+20%), and associative striatum (+17%) rostrally, but was not changed in caudal forebrain. In contrast, delta opioid receptor binding was not significantly altered at any region analyzed, in either nondyskinetic or dyskinetic, MPTP-lesioned macaques, compared to normal. These results suggest that transient changes in delta opioid receptor binding may occur in motor circuits following acute dopamine depletion. However, in the more chronic MPTP-lesioned macaque model, simple changes in delta opioid receptor number or affinity are unlikely to contribute to mechanisms for abnormal opioid transmission in Parkinson's disease and dyskinesia.

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“…Dynorphin-ir and enkephalin-ir neurons are more ubiquitously distributed and found in regions that include basal ganglia, amygdala, cortex, NAC, hypothalamus, brainstem nuclei and spinal cord [100,213,347]. The distribution of opioid receptors measured autoradiographically is generally consistent with terminal field distributions of their corresponding peptides [94,135,199,201,325]. MOR density in the telencephalon and diencephalon is highest in neocortex, caudate-putamen, amygdala, NAC, bed nucleus of the stria terminalis (BNST), habenula and medial thalamus.…”

Section: A Localizationmentioning

confidence: 61%

Regional Differences in Adaptation of CNS Mu Opioid Receptors to Chronic Opioid Agonist Administration

Sim‐Selley¹

2005

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Opioids produce a number of acute effects, notably antinociception and euphoria, whereas chronic use produces tolerance and dependence. Mu opioid receptors (MOR) mediate opioid antinociception and reinforcement and are distributed throughout the CNS in regions consistent with their acute effects, including striatum, thalamus, amygdala, periaqueductal gray (PAG), locus coeruleus (LC), and spinal cord. G-protein-coupled receptor (GPCR) adaptation involves G-protein-coupled receptor kinase (GRK)-mediated receptor phosphorylation with subsequent β-arrestin binding, which uncouples GPCRs from G-protein activation. β-arrestin binding can initiate receptor endocytosis, leading to subsequent degradation or recycling of GPCRs. These processes are reflected experimentally by desensitization (loss of functional response) and downregulation (loss of receptor binding sites). Evaluation of MOR levels following chronic opioid treatment has indicated that MOR downregulation is not required for the expression of tolerance and dependence. In contrast, evaluation of post-receptor events has revealed region-dependent alterations in MOR-G-protein coupling and subsequent effector activity. For example, MOR-mediated G-protein activity and inhibition of adenylyl cyclase are generally decreased in brainstem nuclei following chronic morphine administration, whereas no changes are found in striatum. Similarly, tolerance develops to MOR-mediated potassium channel activation in regions that include LC and PAG. Chronic opioid-mediated effects on adenylyl cyclase affect downstream signaling via regulation of cAMP dependent protein kinase (PKA) and cAMP response element binding protein (CREB), both of which are altered in LC, nucleus accumbens (NAC) and amygdala, regions that might contribute to motivational and physiological signs of withdrawal. Possible explanations for regional differences in MOR adaptation include region-specific co-localization of MOR with signaling proteins and differential distribution of MOR splice variants or oligomers. Moreover, the finding that regional differences exist in neuroadaptation suggests that behavioral adaptations to chronic opioid administration will vary based on the functional neuroanatomy of the MOR system.

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Quantitative light microscopic localization of [3H]naltrindole binding sites in the rat brain

Cited by 17 publications

References 16 publications

Supraspinal delta opioid receptor mRNA levels are not altered in [D‐Ala²]Deltorphin II tolerant mice

Supraspinal delta opioid receptor mRNA levels are not altered in [D‐Ala²]Deltorphin II tolerant mice

Striatal delta opioid receptor binding in experimental models of Parkinson's disease and dyskinesia

Regional Differences in Adaptation of CNS Mu Opioid Receptors to Chronic Opioid Agonist Administration

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Quantitative light microscopic localization of [3H]naltrindole binding sites in the rat brain

Cited by 17 publications

References 16 publications

Supraspinal delta opioid receptor mRNA levels are not altered in [D‐Ala2]Deltorphin II tolerant mice

Supraspinal delta opioid receptor mRNA levels are not altered in [D‐Ala2]Deltorphin II tolerant mice

Striatal delta opioid receptor binding in experimental models of Parkinson's disease and dyskinesia

Regional Differences in Adaptation of CNS Mu Opioid Receptors to Chronic Opioid Agonist Administration

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Supraspinal delta opioid receptor mRNA levels are not altered in [D‐Ala²]Deltorphin II tolerant mice

Supraspinal delta opioid receptor mRNA levels are not altered in [D‐Ala²]Deltorphin II tolerant mice