Abstract: Orexins are neuropeptides produced by the hypothalamus. Orexin neurons have extensive projections to the mesolimbic dopamine system (MLSD) and are critically involved in drug addiction. The central nucleus of the MLSD, the ventral tegmental area (VTA) and nucleus accumbens (NAc), contain abundant orexinergic fibers and receptors. In the VTA, orexins are implicated in drug reward-elicited place preference and acquisition of behavioral sensitization. However, less study has been focused on the role of orexins in the NAc in drug reward by now. The present study aims to investigate the roles of orexins in the VTA and NAc in drug reward-associated behavior.
The development of conditioned place preference (CPP) induced by morphine was used to investigate the roles of orexins in the VTA and NAc in drug reward. The apparatus for the CPP was consisted of two distinctive compartments. The 135 male Wistar rats were alternatively treated with morphine (3mg/kg) or saline before conditioning training (45min), with one injection per day. Before three conditioning sessions with morphine, the OXR1 antagonist SB334867 was bilaterally microinjected into the VTA (0, 1, 5 μg) or NAcSh (0, 1, 3 μg). Before two conditioning sessions with morphine, orexin A (0, 2, 4, 6 μg) was bilaterally microinjected into the NAcSh. One-way ANOVA and Post Hoc LSD were used to reveal the difference among groups.
The results showed that the development of morphine CPP was inhibited when SB334867 was infused into the VTA and not affected when SB334867 was infused into the NAcSh. Orexin A microinjected into the NAcSh did not enhance or inhibit morphine CPP, but increased locomotor activity especially in the rats treated with morphine.
The present study demonstrated the different roles of orexins in the VTA and NAcSh in drug reward induced by morphine, indicating that orexins in these two brain regions might regulate the different aspects of addictive behavior.

Key words: conditioned place preference, orexin, ventral tegmental area, nucleus accumbens, OXR1 antagonist