It has been shown that orexin neuropeptides contribute to morphine-induced physical dependence. The locus coeruleus (LC), which receives a dense extra-hypothalamic orexinergic projection, is a key brain region implicated in the expression of somatic signs of morphine withdrawal syndrome. The aim of the present study is to investigate the role of LC orexin type 1 receptors (OXR1) on naloxone-precipitated morphine withdrawal signs in rats. Adult male Wistar rats were rendered dependent on morphine by subcutaneous (s.c.) injection of morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. On day 10, naloxone (1 mg/kg i.p.) was injected 2 h after morphine administration. Somatic signs of withdrawal were then evaluated in a clear Plexiglas test chamber (30cm diameter, 50cm height) for 25 min. One group of animals received intra-LC SB-334867-A, a selective OXR1 antagonist, (100M, 0.2l) immediately before naloxone. In the control group, SB-334867-A vehicle was microinjected into the LC in the same manner. The results showed that intra-LC OXR1 receptor blockade significantly decreased the somatic signs of withdrawal including chewing, diarrhea, scratching, teeth chattering, wet-dog shake and ptosis. These results suggest that activation of OXR1 in the LC might be involved in the expression of withdrawal signs in morphine dependent rats.
کلید واژگان :Orexin, Orexin type 1 receptor, Locus coeruleus, Naloxone, Morphine withdrawal
ارزش ریالی : 600000 ریال
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