In both the H-RI and L-RI rats, we also measured orexin mRNA levels in the lateral hypothalamus 9 days after heroin self-administration, and found a significant increase in both groups. This is consistent with previous reports showing enhanced orexin gene expression during acute withdrawal from chronic morphine or heroin exposure [20, 21]. Since orexin peptide A has been found to decrease the excitability of brain reward systems in the lateral hypothalamus [44], the alteration of orexin gene expression is likely involved in the negative affective state in heroin withdrawal and abstinence, which may be important in the modulation of drug-seeking behaviors [22, 23].
