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Updated: Jun 21, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Involvement of nitric oxide synthesis in sensitization to the rewarding effects of morphine
Carmen Manzanedo1, María A Aguilar, Bruno Ribeiro Do Couto
1Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, 46010 Valencia, Spain.
Abstract:
Knowledge about the specific brain changes and neural plasticity processes produced by repeated exposure to a drug is essential to progress in the field of neurobiology of addiction and the development of effective medication. In the present study, the influence of nitric oxide synthesis on sensitization to the rewarding effects of morphine has been evaluated. The effects of pre-treatment of mice with saline or 20mg/kg of morphine plus the nitric oxide synthase inhibitor 7-nitroindazole (7NI) (12.5 or 25mg/kg) on the place conditioning induced by a low dose of morphine (2mg/kg) were assessed. The dose of 2mg/kg of morphine was ineffective in animals pre-treated with saline but induced a clear conditioned place preference (CPP) in those pre-treated with morphine. Conversely, animals pre-treated with morphine plus 7NI did not acquire CPP. Our results demonstrate that the nitric oxide pathway is implicated in the development of sensitization to the conditioned rewarding effects of morphine.
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