Drug dependence has been considered as a reoccurred brain disease characterized by persistent pathological craving for addictive drug. How to inhibit the abnormal craving is critical to the clinic treatment of drug addiction. It is well known that hyperthalamus plays a critical role in reward and stress, orexin neurons which were only distributed in the hyperthalamus are in good position to innervate mesolimbic dopamine system and midline thalamus. It suggested that orexin receptors in these brani areas will be involved into drug addiction. In the present series of studies, we aimed to investigate the role of orexin and MCH receptors in the midline thalamus,VTA and nucleus accumbens on the expression of morphine and sexual reward with conditioned place preference (CPP) paradigm. The main results showed that blockade of orexin receptors in VTA impaired the acqusition and expression of morphine-induced morphine CPP,but had no effect on sexual reward and sexual intercourse in male rats. whereas microinjectio of orexin antagonists into NAC inhibited the reinstatement of CPP induced by foot shock, but had no effect on morphine and sexual reward. However, activation of orexin receptor in PVT produced stress and anxiety-like behaiviors in EPM and open field test,and primary results shown that orexin receptors in PVT we
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