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Investigating the Roles of Orexinergic System in Methamphetamine‐induced Addiction
Author(s) -
Lee Chan,
Bae Hui Jin,
Jang Jung-Hee,
Park Gyu Hwan
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09577
Subject(s) - meth , orexin , methamphetamine , orexin receptor , dopamine , dopaminergic , conditioned place preference , addiction , pharmacology , lateral hypothalamus , neuroscience , chemistry , striatum , receptor , medicine , psychology , neuropeptide , hypothalamus , monomer , organic chemistry , acrylate , polymer
Methamphetamine (METH) is a powerful neurotoxic psychostimulant characterized to affects activity of dopamine transpoters leading to blockage of dopamine (DA) uptake into the synaptic vesicle as well as DA reuptake through the plasma membrane inducing synaptic DA release, which resulted in continuous excess extracellular DA levels in the synaptic cleft. Orexinergic system has been reported to play crucial roles in regulation of arousal, wakefulness, and motivated behaviors for drug abuse. In this study, we have investigated the roles of orexin and/or orexin receptors on METH‐induced addictive behaviors by conducting conditioned place preference (CPP) test using SB334867, an orexin‐1 receptor antagonist. The changes in the dopaminergic system integrity and orexin‐related signaling molecules were examined to elucidate underlying molecular mechanisms. C57BL/6 mice were administered with METH (1 mg/kg, i.p.) alternately on each other day for 8 days, allowed to undergo withdrawal period without injection of METH for additional 8 days, and then challenged again with METH. METH‐administered mice exhibited increased levels of orexin and orexin‐1 receptor in the brain regions of hippocampus, striatum, hypothalamus, and amygdala. The application of SB334867 significantly attenuated the acquisition, expression, and reinstatement of the METH‐induced CPP. These findings suggest that orexinergic system may play a role in the acquisition and relapse of METH‐induced addictive behaviors, thereby providing a novel therapeutic target for the METH addiction. Support or Funding Information This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)