Orexin neuropeptides have been reported to be involved in morphine induced physical dependence andwithdrawal. The Lateral Paragigantocellularis (LPGi) is a key brain region implicated in the expression ofsomatic signs of morphine withdrawal syndrome. Orexin A and orexin type 1 receptor have been found inLPGi neurons but the effect of orexin on the expression of opiate dependence and withdrawal phenomenain this brain structure has not been studied yet. In this study, the effect of intra-LPGi administration ofSB 334867 (selective orexin type 1 receptor antagonist) on the behavioral signs of morphine withdrawalsyndrome was investigated. Male Wistar rats weighing 250–300 g were rendered dependent by addingmorphine sulfate (Temad, Tehran, Iran) to their drinking water in increasing concentrations of 0.1, 0.2,0.3 mg/ml for every 48 h and 0.4 mg/ml during the next 15 days. Behavioral signs of morphine with-drawal were assessed in a transparent cylindrical Plexiglas test chamber (30 cm diameter, 50 cm height)for 25 min. One group of animals received intra-LPGi injection of SB 334867 (0.2 l, 100 M) immediatelybefore naloxone. In the control group, SB-334867 vehicle (DMSO 1%, 0.2 l) was microinjected into LPGi.Our results indicate that intra-LPGi administration of SB 334867 significantly decreases naloxone precip-itated morphine withdrawal signs. Thus, it seems that orexin might have a pivotal role in the expressionof morphine withdrawal signs through affecting orexin type 1 receptor in LPGi nucleus.
کلید واژگان :Morphine withdrawal, Orexin type 1 receptor, SB-334867, LPGi
ارزش ریالی : 1200000 ریال
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