Role of orexin-1 and orexin-2 receptors in the CA1 region of hippocampus in the forced swim stress- and food deprivation-induced reinstatement of morphine seeking behaviors in rats

• Published in: Brain research bulletin 2018-09, Vol.142, p.25-32
• Main Authors: Edalat, Pariya, Kavianpour, Mohadeseh, Zarrabian, Shahram, Haghparast, Abbas
• Format: Article
• Language: English
• Subjects: Animals; Benzoxazoles - pharmacology; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - metabolism; Drug-Seeking Behavior - physiology; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Food deprivation; Food Deprivation - physiology; Forced swim stress; Hippocampus; Isoquinolines - pharmacology; Male; Morphine Dependence - metabolism; Neurons - drug effects; Neurons - metabolism; Orexin Receptor Antagonists - pharmacology; Orexin Receptors - metabolism; Orexinergic system; Pyridines - pharmacology; Rat; Rats, Wistar; Reinstatement; Reward; Stress; Stress, Psychological - metabolism; Swimming - physiology; Urea - analogs & derivatives; Urea - pharmacology
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2018.06.016

•Orexin receptors have an important role in inducing the reinstatement phase of morphine CPP.•Activation of orexinergic neurons in the CA1 potentiates the effect of acute stress on reinstatement to morphine.•Administration of SB334867 into the CA1 was more effective in reducing FSS comparing to FD.•Intra-CA1 administration of TCSOX2 29 had a similar decreasing effect on the FSS and FD. Hippocampus (HIP) is an essential brain site to study reward-related learning tasks, such as conditioning place preference (CPP) that can measure the preference for environmental stimuli related to reward. Furthermore, orexin neurons, situated exclusively in the lateral hypothalamus (LH) and link the rewarding effects of drugs of abuse in the LH and the CA1 region of the HIP. Therefore, in this study adult male rats were conditioned with morphine using a CPP paradigm. After the eighth day of the extinction period, on the reinstatement day, orexin-1 and orexin-2 receptor antagonists were administered bilaterally into the CA1 region prior to acute stress. Using two different types of acute stress, forced swim stress (FSS) and food deprivation (FD), the role of orexin-1 and orexin-2 receptors in the CA1 brain region in FSS and FD induced reinstatement was investigated. Our results showed that application of the orexin-1 and orexin-2 antagonists, SB334867 and TCSOX2 29, respectively, reduced the CPP scores in the reinstatement phase. Moreover, it can be concluded that orexin neurons are activated in acute stress states, such as FSS and FD, as blocking the orexin receptors, decreased the effects of acute stress in triggering the reinstatement of morphine-CPP.