首页|Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System

Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System

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Opioid use disorder(OUD)has become a con-siderable global public health challenge;however,potential medications for the management of OUD that are effective,safe,and nonaddictive are not available.Accumulating pre-clinical evidence indicates that antagonists of the dopamine D3 receptor(D3R)have effects on addiction in different animal models.We have previously reported that YQA14,a D3R antagonist,exhibits very high affinity and selectiv-ity for D3Rs over D2Rs,and is able to inhibit cocaine-or methamphetamine-induced reinforcement and reinstatement in self-administration tests.In the present study,our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-admin-istered rats,also attenuated heroin-induced reinstatement of drug-seeking behavior.On the other hand,YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice.Moreover,we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibit-ing morphine-induced up-regulation of dopaminergic neu-ron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber pho-tometry recording system.These findings suggest that D3R might play a very important role in opioid addiction,and YQA14 may have pharmacotherapeutic potential in attenu-ating opioid-induced addictive behaviors dependent on the dopamine system.

Opioid use disorderD3 receptorsDopamineSelf-administrationConditioned place preference

Rong-Rong Hu、Meng-Die Yang、Xiao-Yan Ding、Ning Wu、Jin Li、Rui Song

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State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Key Laboratory of Neuropsychopharmacology,Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China

Department of Nuclear Medicine,Hainan Hospital of Chinese PLA General Hospital,Sanya 572013,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of BeijingNational Key R&D Program of ChinaNational Key R&D Program of ChinaMedical Innovation ProgramBeijing Nova Program

81573405U150222572121592016YFC08009072017YFC13104016CXZ033xx2014A014

2023

10.1007/s12264-023-01059-0

神经科学通报(英文版)
中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD
影响因子：0.741
ISSN：1673-7067
年,卷(期)：2023.39(11)
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