Nucleus accumbens hyperpolarization-activated cyclic nucleotide-gated channels modulate methamphetamine self-administration in rats

被引:14
作者
Cao, Dan-Ni [1 ]
Song, Rui [1 ]
Zhang, Shu-Zhuo [1 ]
Wu, Ning [1 ]
Li, Jin [1 ]
机构
[1] Beijing Inst Pharmacol & Toxicol, State Key Lab Toxicol & Med Countermeasures, Beijing Key Lab Neuropsychopharmacol, 27th Taiping Rd, Beijing 100850, Peoples R China
基金
中国国家自然科学基金;
关键词
Methamphetamine; Dopamine; Hyperpolarization-activated cyclic nucleotide-gated channels; In vivo microdialysis; Nucleus accumbens; Self-administration; D-3 RECEPTOR ANTAGONIST; DRUG-SEEKING BEHAVIOR; CURRENT I-H; HCN CHANNELS; PHARMACOLOGICAL TARGET; DOPAMINERGIC-NEURONS; ADDICTION; YQA14; RELEASE; KINASE;
D O I
10.1007/s00213-016-4349-z
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Methamphetamine addiction is believed to primarily result from increased dopamine release and the inhibition of dopamine uptake. Some evidence suggests that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in the functional modulation of dopaminergic neurons and the pathophysiology of related diseases. However, little is known about the effects of HCN channels on methamphetamine addiction. The present study investigated the role of brain HCN channels in methamphetamine addiction. Acute intracerebroventricular (i.c.v.) injection or bilateral intra-accumbens microinjections of non-selective HCN channel blocker ZD7288 (0.3125 and 0.625 mu g) significantly reduced both methamphetamine (0.0125 or 0.05 mg/kg/infusion)-induced self-administration under fixed ratio 2 reinforcement and the breakpoint of methamphetamine (0.05 mg/kg/infusion) under progressive ratio reinforcement in rats. Moreover, compared with i.c.v. injection, bilateral intra-accumbens microinjections of ZD7288 exerted stronger inhibitory effects, suggesting that blockade of HCN channels in the nucleus accumbens reduced the reinforcing effects of and motivation for methamphetamine. We also found that ZD7288 (0.625 and 1.25 mu g, i.c.v.) significantly decreased methamphetamine (1 mg/kg, intraperitoneal (i.p.))-induced hyperactivity with no effect on the spontaneous activity in rats. Finally, in vivo microdialysis experiments showed that the HCN channel blockade using ZD7288 (0.625 and 1.25 mu g, i.c.v.) decreased methamphetamine (1 mg/kg, i.p.)-induced elevation of extracellular dopamine levels in the nucleus accumbens. These results indicate that HCN channels in the nucleus accumbens are involved in the reinforcing properties of methamphetamine and highlight the importance of HCN channels in the regulation of dopamine neurotransmission underlying methamphetamine addiction.
引用
收藏
页码:3017 / 3029
页数:13
相关论文
共 48 条
[41]   YQA14: a novel dopamine D3 receptor antagonist that inhibits cocaine self-administration in rats and mice, but not in D3 receptor-knockout mice [J].
Song, Rui ;
Yang, Ri-Fang ;
Wu, Ning ;
Su, Rui-Bin ;
Li, Jin ;
Peng, Xiao-Qing ;
Li, Xia ;
Gaal, Jozsef ;
Xi, Zheng-Xiong ;
Gardner, Eliot L. .
ADDICTION BIOLOGY, 2012, 17 (02) :259-273
[42]   A selective D3 receptor antagonist YQA14 attenuates methamphetamine-induced behavioral sensitization and conditioned place preference in mice [J].
Sun, Li ;
Song, Rui ;
Cheg, Ying ;
Yang, Ri-fang ;
Wu, Ning ;
Su, Rui-bin ;
Li, Jin .
ACTA PHARMACOLOGICA SINICA, 2016, 37 (02) :157-165
[43]   CATION CURRENT ACTIVATED BY HYPERPOLARIZATION IN A SUBSET OF RAT NUCLEUS-ACCUMBENS NEURONS [J].
UCHIMURA, N ;
CHERUBINI, E ;
NORTH, RA .
JOURNAL OF NEUROPHYSIOLOGY, 1990, 64 (06) :1847-1850
[44]   Addiction: Beyond dopamine reward circuitry [J].
Volkow, Nora D. ;
Wang, Gene-Jack ;
Fowler, Joanna S. ;
Tomasi, Dardo ;
Telang, Frank .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (37) :15037-15042
[45]   Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih [J].
Wanat, M. J. ;
Hopf, F. W. ;
Stuber, G. D. ;
Phillips, P. E. M. ;
Bonci, A. .
JOURNAL OF PHYSIOLOGY-LONDON, 2008, 586 (08) :2157-2170
[46]   Brain cannabinoid CB2 receptors modulate cocaine's actions in mice [J].
Xi, Zheng-Xiong ;
Peng, Xiao-Qing ;
Li, Xia ;
Song, Rui ;
Zhang, Hai-Ying ;
Liu, Qing-Rong ;
Yang, Hong-Ju ;
Bi, Guo-Hua ;
Li, Jie ;
Gardner, Eliot L. .
NATURE NEUROSCIENCE, 2011, 14 (09) :1160-U216
[47]   Effects of thienorphine on release of dopamine and noradrenalin: An in vivo microdialysis study in rats [J].
Yong, Zheng ;
Yan, Lingdi ;
Zhou, Peilan ;
Yu, Gang ;
Dong, Huajing ;
Gong, Zehui .
NEUROSCIENCE LETTERS, 2012, 513 (02) :132-136
[48]   Activity-dependent heteromerization of the hyperpolarization-activated, cyclic-nucleotide gated (HCN) channels: role of N-linked glycosylation [J].
Zha, Qinqin ;
Brewster, Amy L. ;
Richichi, Cristina ;
Bender, Roland A. ;
Baram, Tallie Z. .
JOURNAL OF NEUROCHEMISTRY, 2008, 105 (01) :68-77