THE EFFECTS OF HEROIN ON THE EXPRESSION OF Μ-OPIOID RECEPTORS, Κ-OPIOID RECEP- TORS AND CREB PATHWAY-RELATED MOLECULES IN THE VENTRAL TEGMENTAL AREA AND THE NUCLEUS ACCUMBENS OF RATS

YAN HONG, YI-XIN LI, WEN-MEI LIANG

Laboratory of Histology and Embryology, School of Basic Medical Science, Guizhou Medical University, Guian New Area, Guizhou 550025, China

Objective: To investigate changes in the expression of μ-opioid receptors (MORs), κ-opioid receptors (KORs), and cyclic adenosi- ne monophosphate response element-binding protein (CREB) pathway-related molecules in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) during heroin dependence. We induced heroin dependence in male Sprague-Dawley rats, and immunohisto- chemistry, western blotting, and Real-time PCR were used to examine the protein and messenger RNA (mRNA) expression levels of MOR, KOR, and CREB pathway-related molecules. In the VTA, protein and mRNA expression of MOR were initially depressed but later elevated due to treatment of heroin. Protein and mRNA expression of KOR did not change significantly between days 10 and 24 in the heroin-dependent group, but it was significantly elevated after treatment for 31days. Heroin dependence increased the protein and mRNA expression of protein kinase A (PKA) and phosphorylated CREB. In the NAc, heroin reduced the protein and mRNA expression of MOR with slight fluctuations. 10 and 17 days of treatment with heroin induced highly expressed KOR at protein and mRNA level, but 24 and 31 days of treatment with heroin did not affect the expression of KOR. In addition, 17 days of treatment heroin upregulated the pro- tein expression of PKA and phosphorylated CREB, increased mRNA of PKA and CREB was also induced by heroin. Our study demon- strated that heroin dependence not only affected MOR and KOR expression in the VTA and NAc, but also increased the expression of downstream CREB pathway molecules.