Blockade of orexin receptors in the hippocampal dentate gyrus reduced the extinction latency of morphine-induced place preference in male rats. 2021

Kimia RayatSanati, and Shole Jamali, and Amir Arash Hassanlou, and Abbas Haghparast
Student Research Committee, Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Relapse to drugs such as opioids is a major challenge in addiction therapy. It has been known that the orexinergic system has a significant role in mediating reward processing and addiction, as shown by the conditioned place preference (CPP). The dentate gyrus (DG) of the hippocampus receives orexinergic projections from the lateral hypothalamus that has been approved as a critical area arbitrating the maintenance of drug-seeking behavior following the extinction. The present study aimed to investigate the effects of intra-DG administration of the orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) antagonists on the extinction of morphine-induced CPP in male rats. Animals received different doses of SB334867 (as OX1R antagonist) or TCS OX2 29 (as OX2R antagonist) (0.5, 2.5, and 12.5 nM/0.5 μl DMSO 12 %) bilaterally into the DG during the extinction phase, after CPP had been induced by subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase. The conditioning scores were recorded during the test. The results demonstrated that intra-DG administration of the highest dose of OX1R antagonist (12.5 nM/0.5 μl DMSO 12 %) shortened the extinction latency of morphine-CPP compared to the DMSO group, while the OX2R antagonist did not significantly alter the latency. Findings imply that the blockade of OX1R, but not OX2R, within the DG facilitates the extinction of morphine-induced reward. In conclusion, the OX1R antagonist might be kept in mind as a convenient therapeutic factor in repressing drug-seeking behaviors in an optimum amount of treatment considering the low dose-treatments applied.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008297 Male Males
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009287 Naphthyridines A group of two-ring heterocyclic compounds consisting of a NAPHTHALENES double ring in which two carbon atoms, one per each ring, are replaced with nitrogens.
D009294 Narcotics Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS. Analgesics, Narcotic,Narcotic Analgesics,Narcotic,Narcotic Effect,Narcotic Effects,Effect, Narcotic,Effects, Narcotic
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D003216 Conditioning, Operant Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced. Instrumental Learning,Learning, Instrumental,Operant Conditioning,Conditionings, Operant,Instrumental Learnings,Learnings, Instrumental,Operant Conditionings
D005108 Extinction, Psychological The procedure of presenting the conditioned stimulus without REINFORCEMENT to an organism previously conditioned. It refers also to the diminution of a conditioned response resulting from this procedure. Psychological Extinction,Extinction (Psychology),Extinctions (Psychology),Extinctions, Psychological,Psychological Extinctions
D000068796 Orexin Receptor Antagonists Substances that bind to and inhibit the action of OREXIN RECEPTORS. Drugs in this class have been used as SLEEP AIDS, PHARMACEUTICAL. Dual Orexin Receptor Antagonist,Orexin Receptor Antagonist,Dual Orexin Receptor Antagonists,Orexin Receptor Blockers,Antagonist, Orexin Receptor,Receptor Antagonist, Orexin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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