Sigma receptor agonists: receptor binding and effects on mesolimbic dopamine neurotransmission assessed by microdialysis.
Sigma receptor agonists: receptor binding and effects on mesolimbic dopamine neurotransmission assessed by microdialysis.
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DOI：
10.1016/j.biopsych.2010.07.026
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发表时间：
2011-02-01
影响因子：
10.6
通讯作者：
Tanda, Gianluigi
中科院分区：
文献类型：
--
作者：
Garces-Ramirez, Linda;Green, Jennifer L.;Hiranita, Takato;Kopajtic, Theresa A.;Mereu, Maddalena;Thomas, Alexandra M.;Mesangeau, Christophe;Narayanan, Sanju;McCurdy, Christopher R.;Katz, Jonathan L.;Tanda, Gianluigi
关键词：
σ（σ）受体的两种亚型σ1和σ2可以被清楚地区分，并且每一种都可能涉及物质滥用障碍。σ-受体拮抗剂阻断可卡因位置条件反射，并且在先前自我施用可卡因的大鼠中自我施用σ-受体激动剂。对于不同的药物类别，自我给药与多巴胺（DA）神经传递增加有关。σ-受体激动剂对中脑边缘DA的作用尚未完全表征。受体结合研究评估了不同σ受体配体对σ受体亚型和DA转运蛋白的亲和力;使用体内微透析评估了对大鼠延髓核壳中DA传递的影响。钴（0.1-1.0 mg/kg i.v.），非选择性σ1/2受体激动剂DTG（1.0-5.6 mg/kg i. v.），和选择性σ1-受体激动剂PRE-084（0.32-10 mg/kg i. v.）剂量依赖性地增加DA，最大值分别为约275、150和160%。DTG诱导的DA兴奋可被非选择性σ1/2受体拮抗剂BD 1008（10 mg/kg i. p.）和优选的σ2-受体拮抗剂SN 79（1-3 mg/kg i. p.），但不被优选的σ1受体拮抗剂BD 1063（10-30 mg/kg i. p.）PRE-084和可卡因均未被BD 1063或BD 1008拮抗。证明了在参与可卡因强化作用的脑区中通过σ受体激动剂刺激DA。这种效应似乎是由σ2受体而不是σ1受体介导的。然而，σ受体不太可能参与介导DA传递的急性可卡因和PRE-084诱导的刺激。不同的机制可能是σ-受体激动剂的多巴胺能和增强作用的基础，表明可能导致物质滥用障碍的多巴胺非依赖性增强途径。
Two subtypes of sigma (σ) receptors, σ1 and σ2, can be pharmacologically distinguished, and each may be involved in substance-abuse disorders. σ-receptor antagonists block cocaine place conditioning and σ-receptor agonists are self-administered in rats that previously self-administered cocaine. Self-administration has been related to increased dopamine (DA) neurotransmission for different drug classes. Actions of σ-receptor agonists on mesolimbic DA have not been fully characterized. Receptor-binding studies assessed affinities of different σ-receptor ligands for σ-receptor subtypes, and for the DA transporter; effects on DA transmission in the rat nucleus accumbens shell were assessed using in-vivo microdialysis. Cocaine (0.1–1.0 mg/kg i.v.), the non-selective σ1/2-receptor agonist DTG (1.0–5.6 mg/kg i.v.), and the selective σ1-receptor agonist PRE-084 (0.32–10 mg/kg i.v.) dose-dependently increased DA, with maxima of about 275, 150, and 160%, respectively. DTG-induced stimulation of DA was antagonized by the nonselective σ1/2-receptor antagonist, BD 1008 (10 mg/kg i.p.), and by the preferential σ2-receptor antagonist SN79 (1–3 mg/kg i.p.), but not by the preferential σ1-receptor antagonist, BD 1063 (10–30 mg/kg i.p.). Neither PRE-084 nor cocaine was antagonized by either BD1063 or BD1008. Stimulation of DA by σ-receptor agonists in a brain area involved in the reinforcing effects of cocaine was demonstrated. The effects appear to be mediated by σ2-receptors rather than σ1-receptors. However σ-receptors are not likely involved in mediating the acute cocaine- and PRE-084-induced stimulation of DA transmission. Different mechanisms might underlie the dopaminergic and reinforcing effects of σ-receptor agonists suggesting a dopamine-independent reinforcing pathway that may contribute to substance-abuse disorders.
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影响因子：
4.7
作者：
Matsumoto, RR;McCracken, KA;Bowen, WD
通讯作者：
Bowen, WD
DOI：
10.1073/pnas.93.15.8072
发表时间：
1996-07-23
影响因子：
11.1
作者：
Hanner, M;Moebius, FF;Glossmann, H
通讯作者：
Glossmann, H
影响因子：
13.5
作者：
Maurice T;Su TP
通讯作者：
Su TP
影响因子：
7.3
作者：
Maurice, T;Phan, VL;Nabeshima, T
通讯作者：
Nabeshima, T
DOI：
10.1016/0922-4106(94)90115-5
发表时间：
1994-06-15
期刊：
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION
影响因子：
--
作者：
HELLEWELL, SB;BRUCE, A;BOWEN, WD
通讯作者：
BOWEN, WD