Synergistic antinociceptive actions and tolerance development produced by morphine-fentanyl coadministration: Correlation with mu-opioid receptor internalization


Por: Silva-Moreno A., Gonzalez-Espinosa C., León-Olea M., Cruz S.L.

Publicada: 15 ene 2012
Categoría: Pharmacology

Resumen:
It has been described that coadministration of opioids with low doses of other analgesics can reduce adverse effects and increase antinociception, but combinations of two mu-opioid receptor agonists have been poorly explored. The objective of this work was threefold: 1) to evaluate the antinociceptive combination of i.c.v. morphine and fentanyl at different doses; 2) to compare the antinociception produced by acute or repeated administration of an effective morphine dose (1 mu g) alone, or combined with a low fentanyl dose (1 g); and 3) to correlate these effects with mu-opioid receptor internalization in periaqueductal gray matter and locus coeruleus. Antinociception was evaluated by the tail-flick test and receptor internalization was analyzed by confocal microscopy in Wistar rats. Drug interactions were examined by administering combinations of opioids in 1:3,1:1 and 3:1 ratios of their respective ED50 fractions. For tolerance and internalization studies, animals were i.c.v. injecte

Filiaciones:
Silva-Moreno A.:
 Departamento de Farmacobiología, Cinvestav, Sede Sur, Calzada de los Tenorios # 235, Col. Granjas Coapa, México D.F., 14330, Mexico

Gonzalez-Espinosa C.:
 Departamento de Farmacobiología, Cinvestav, Sede Sur, Calzada de los Tenorios # 235, Col. Granjas Coapa, México D.F., 14330, Mexico

León-Olea M.:
 Departamento de Neuromorfología Funcional, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada Mexico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, México D.F. 14370, Mexico

Cruz S.L.:
 Departamento de Farmacobiología, Cinvestav, Sede Sur, Calzada de los Tenorios # 235, Col. Granjas Coapa, México D.F., 14330, Mexico

 Departamento de Neuromorfología Funcional, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calzada Mexico-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, México D.F. 14370, Mexico
ISSN: 00142999
Editorial
ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS, Países Bajos
Tipo de documento: Article
Volumen: 674 Número: 2-3
Páginas: 239-247
WOS Id: 000300200000021
ID de PubMed: 22079772