Involvement of central endothelin receptors in neonatal morphine withdrawal.
Exp Biol Med (Maywood)
; 231(6): 1157-60, 2006 Jun.
Article
en En
| MEDLINE
| ID: mdl-16741068
The involvement of central endothelin (ET) receptors in neonatal morphine tolerance has been demonstrated. The present study investigates the role of central ET receptors in morphine withdrawal in neonatal rats. The aim was to determine whether activation of G-proteins coupled to opioid and ET receptors by morphine and various ET receptor modulators is affected during morphine withdrawal in neonatal rats. Pregnant female rats were rendered tolerant to morphine by chronic exposure to morphine pellets during 7 days. On Day 8, pellets were removed and rats were allowed to undergo withdrawal for 24 hrs. Rat pups were delivered by cesarean section. G-protein stimulation induced by morphine; ET-1; the ET(A) receptor antagonist, BMS182874; and the ET(B) receptor agonist, IRL1620, were determined in the brain of neonatal rats undergoing morphine withdrawal by [35S]GTPgammaS binding assay. Morphine produced higher (P < 0.05) maximal stimulation of G-protein in the morphine-withdrawal group (83.60%) compared with the placebo group (66.81%). ET-1-induced G-protein stimulation was also altered, and the median effective concentration (EC50) during morphine withdrawal (170.60 nM) was significantly higher than placebo (62.5 nM; P< 0.05). The maximal stimulation induced by the ET(A) receptor antagonist, BMS182874, in the morphine-withdrawal group (86.07%; EC50 = 31.25 nM) was significantly higher than in the placebo group (EC50 > 1000 nM). The ET(B) agonist, IRL1620, induced G-protein stimulation was similar in placebo (73.43%, EC50 = 13.26 nM) and morphine-withdrawal groups (75.08%, EC(50) = 11.70 nM), respectively. To our knowledge, this is the first report indicating involvement of central ET(A) receptors in neonatal morphine withdrawal.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Abstinencia a Sustancias
/
Sistema Nervioso Central
/
Antagonistas de los Receptores de la Endotelina A
/
Analgésicos Opioides
/
Morfina
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Exp Biol Med (Maywood)
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
/
MEDICINA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido