Abstract
Orexins are found to participate in mediating stress-induced drug relapse. However, the neuroanatomical basis that orexin transmission modulates stress-induced drug seeking remains unknown. The nucleus accumbens shell (NAcSh), best known for its role in appetitive and negative motivation via dopamine receptors, is likely to be the potential important brain area where the orexin system mediates stress-induced drug relapse since the function of dopamine system in the NAcSh can be regulated by orexin transmission. In the present study, a morphine conditioned place preference (CPP) model was used to determine whether the two types of orexin receptors would be involved into footshock-induced and/or drug priming-induced CPP reinstatement differentially. The results showed that blockade of orexin-1 or orexin-2 receptor in the NAcSh significantly attenuated stress-induced morphine CPP reinstatement, but neither of the orexin antagonists had any effect on morphine priming-induced reinstatement. These findings indicate that the NAcSh is a brain area through which orexins participate in stress but not drug priming-induced relapse of opioid seeking.
Highlights
Orexins, including orexin A (OXA) and orexin B (OXB), are neuropeptides derived exclusively from a small group of neurons in the lateral and perifornical areas of the posterior hypothalamus
Recent studies have demonstrated an important role for the orexin system in relapse to drugs of abuse, especially to cocaine and alcohol, but little is known about the role of orexins in opioid relapse (Plaza-Zabala et al, 2012)
We found that footshock stress and morphine challenge significantly reinstated the extinguished morphine conditioned place preference (CPP)
Summary
Orexins, including orexin A (OXA) and orexin B (OXB), are neuropeptides derived exclusively from a small group of neurons in the lateral and perifornical areas of the posterior hypothalamus. The specific role of orexin receptors in drug reward and reinforcement remains controversial (Borgland et al, 2006; Smith et al, 2009; Shoblock et al, 2011; Voorhees and Cunningham, 2011; Plaza-Zabala et al, 2012), but it is quite clear that the orexin system was involved into different types of drug seeking induced by stress, cue and context associated with drug reinforcement (Boutrel et al, 2005; Dayas et al, 2008; Smith et al, 2010). It indicates that orexin transmission may uniquely modulate drug relapse-like behaviors but may not play a key role in the reinforcement of drugs of abuse that maintains the ongoing drug taking behaviors
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