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α-Pinene Attenuates Methamphetamine-Induced Conditioned Place Preference in C57BL/6 Mice

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Author(s)
Chan LeeJung-Hee JangGyu Hwan Park
Keimyung Author(s)
Jang, Jung Hee
Department
Dept. of Pharmacology (약리학)
Journal Title
Biomol Ther
Issued Date
2023
Volume
31
Issue
4
Keyword
ApoptosisConditioned place preferenceInflammationMethamphetamineOxidative Stressα-Pinene
Abstract
Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.
Keimyung Author(s)(Kor)
장정희
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
2005-4483
Source
https://www.biomolther.org/journal/view.html?volume=31&number=4&spage=411&year=2023
DOI
10.4062/biomolther.2022.132
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/45031
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pharmacology (약리학)
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