μ-Opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia
Autor: | Bogdan Sadowski, John C. Liebeskind, John K. Belknap, Jeffrey S. Mogil, Przemyslaw Marek, Melinda L. Helms, L. A. O'Toole |
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Rok vydání: | 1994 |
Předmět: |
Male
medicine.medical_specialty Candidate gene Ratón Central nervous system Analgesic Receptors Opioid mu Mice Inbred Strains Mice Downregulation and upregulation Stress Physiological Internal medicine medicine Animals Tissue Distribution Selection Genetic Receptor Molecular Biology Analysis of Variance Naloxone Chemistry General Neuroscience Brain Up-Regulation Endocrinology medicine.anatomical_structure Morphine Autoradiography Female Neurology (clinical) Analgesia Opiate Neuroscience Developmental Biology medicine.drug |
Zdroj: | Brain Research. 653:16-22 |
ISSN: | 0006-8993 |
DOI: | 10.1016/0006-8993(94)90366-2 |
Popis: | Pain perception and sensitivity to opiate analgesics strongly depend on genotype. Mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia display markedly divergent morphine analgesia, a difference that appears to be determined by one or at the most two major genes. In an attempt to provide candidate genes mediating the supranormal analgesia displayed by HA mice, we performed μ-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [ 3 H]naloxone. HA mice were found to have significantly higher whole-brain receptor density ( B max ) than LA mice in whole brain homogenates; no significant difference in affinity ( K d ) was observed. Quantitative autoradiography confirmed the line difference in whole-brain receptor binding. In the medial thalamus, a brain area implicated in ascending pathways of pain inhibition, HA mice were found to display significantly higher [ 3 H]naloxone binding than C mice (a 64% increase) and LA mice (a 128% increase). No significant line differences were observed in any other brain locus. Thalamic μ receptors may therefore play an important role in a central ‘volume control’ mechanism of pain inhibition, and underlie individual differences in the responses of mice to opiate analgesic drugs. |
Databáze: | OpenAIRE |
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