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Decrease of morphine‐induced reward effects and withdrawal symptoms in mice overexpressing γ‐aminobutyric acid transporter I
Author(s) -
Hu JiaHua,
Yang Na,
Ma YingHua,
Zhou XiaoGang,
Zhang XuYing,
Jiang Jie,
Mei ZhenTong,
Fei Jian,
Guo LiHe
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10780
Subject(s) - morphine , gabaergic , pharmacology , conditioned place preference , addiction , transporter , (+) naloxone , gaba transporter , aminobutyric acid , gamma aminobutyric acid , chemistry , medicine , endocrinology , psychology , opioid , neuroscience , inhibitory postsynaptic potential , receptor , biochemistry , gene
Morphine addiction has been shown to result from neural adaptations produced by repeated drug exposure, but the mechanism is still unclear. In the present study, we found that γ‐aminobutyric acid (GABA) uptake was increased in mouse brain 120 min after, but not 20 min after, morphine (10 mg/kg, s.c.) injection. We generated GABA transporter I (GAT1)‐overexpressing mice to investigate whether the GABAergic system and GABA transporter are involved in morphine‐induced reward effects and withdrawal symptoms. Our results revealed that the rewarding effects induced by morphine were significantly decreased in GAT1‐overexpressing mice as measured by the conditioned place preference (CPP) paradigm. Moreover, both somatic and vegetative signs of naloxone‐induced morphine withdrawal symptoms were substantially reduced in GAT1‐overexpressing mice. In addition, the decreased morphine rewarding in transgenic mice could be recovered when mice were coinjected with NO‐711 (a GAT1 selective inhibitor) in the CPP paradigm. These findings suggest that the GABAergic system plays an important role in morphine addiction and point to the possibility of developing drugs that target GAT1 and extend the clinical application of opiates. © 2003 Wiley‐Liss, Inc.