Overexpression of Type 7 Adenylyl Cyclase in the Mouse Brain Enhances Acute and Chronic Actions of Morphine
| Autor: | Paula L. Hoffman, Masami Yoshimura, Boris Tabakoff, Peter H. Wu |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Narcotics
Genetically modified mouse Transgene Analgesic Mice Transgenic Physical dependence Pharmacology Adenylyl cyclase Mice chemistry.chemical_compound medicine Animals Humans Sensitization Pain Measurement Dose-Response Relationship Drug Morphine business.industry Brain Mice Inbred C57BL medicine.anatomical_structure chemistry Opioid Molecular Medicine medicine.symptom business Adenylyl Cyclases medicine.drug |
| Zdroj: | Molecular Pharmacology. 58:1011-1016 |
| ISSN: | 1521-0111 0026-895X |
| DOI: | 10.1124/mol.58.5.1011 |
| Popis: | The mechanisms by which morphine-induced analgesia and tolerance and physical dependence on morphine arise have been the subject of intense study, and much work has pointed to the involvement of cAMP-mediated events in the neuroadaptive phenomena leading to morphine tolerance and/or dependence. We overexpressed an opioid receptor-stimulatable form of adenylyl cyclase (type 7) in the central nervous system of mice and demonstrated significant effects of this manipulation on the animals9 acute response to morphine, the development of morphine tolerance, and development of sensitization to morphine. Measurements of the acute analgesic response to morphine demonstrated that the ED50 values for the transgenic mice were significantly lower than the ED50 values determined for the “wild-type” animals. During chronic treatment with morphine, the transgenic mice developed tolerance more rapidly than the wild-type mice, and transgenic animals of the C57BL/6xSJL background showed a larger sensitization to morphine9s effects on locomotor activity than did wild-type mice of the same background. These results indicated that cAMP-generating systems may simultaneously modulate the development of tolerance and sensitization. Interestingly, the signs of physical dependence on morphine in the transgenic mice did not differ from those in their wild-type litter mates, indicating that separate mechanisms may modulate opiate tolerance and opiate dependence. |
| Databáze: | OpenAIRE |
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