Involvement of orexin-1 receptor antagonist within the nucleus accumbens, in the effect of forced swim stress on the reinstatement of morphine seeking behaviors

Background and Aim : The high rate of relapse to drug use following drug administration and exposure to stress in addicted individuals is a major clinical problem in drug abuse and addiction treatment. Nevertheless, the mechanisms underlying drug relapse are not completely known. Orexinergic system is involved in primary rewards; the neural circuit of the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex and amygdala represents overlapping elements mediating the rewarding effects of drugs and stressful experiences. The NAc integrates reward-related information from the VTA. Also, it has been indicated that orexinergic system activates the mesolimbic dopamine projecting neurons to the NAc and promotes the development of reward in rodents. Therefore, the aim of this study was to determine the effect of administration of orexin-1 receptor (OX1R) antagonist, into the NAc on the drug-priming and Forced-Swim Stress (FSS)-induced reinstatement of morphine CPP.Methods : In the current study, the conditioned place preference (CPP) paradigm was used to determine the role of orexin 1 receptors (OX1R) in the NAc in forced swim stress (FSS), as physical stress, and/or priming-induced reinstatement of morphine. The CPP was induced by injecting morphine (5mg/kg, SC for 3 days) and lasted for eight free-morphine days; the reinstatement was induced by administration of effective priming dose of morphine (1mg/kg; sc). The extinguished rats received intra-NAc injection of SB334867 as OX1R antagonist before effective priming dose injection of morphine (1mg/kg; sc). In others, the extinguished rats were given intra-NAc injection of SB334867 and then, they underwent FSS before injection of ineffective priming dose of morphine (0.5mg/kg; sc).Results : Our results showed that intra accumbal administration of SB334867 could inhibit morphine priming-and FSS-induced reinstatement of extinguished morphine-seeking in the rats.Conclusion : It seems that OX1R in the NAc may be involved in reward and could play an important role in the effect of stress on reinstatement of morphine-seeking behaviors in this area.

کلیدواژه ها:

Reward ، stress ، orexin system ، nucleus accumbens ، forced swim stress ، conditioned place preference