Orexin type 1 receptor antagonism in Lateral Paragigantocellularis nucleus attenuates naloxone precipitated morphine withdrawal symptoms in rats

Abstract

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