Blockade of adenosine and dopamine receptors inhibits the development of rapid tolerance to ethanol in mice
Blockade of adenosine and dopamine receptors inhibits the development of rapid tolerance to ethanol in mice
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DOI：
10.1007/s00213-005-0014-7
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发表时间：
2005-10-01
影响因子：
3.4
通讯作者：
Takahashi, RN
中科院分区：
文献类型：
--
作者：
Batista, LC;Prediger, RDS;Takahashi, RN
理由：一些报告表明，大脑腺苷和多巴胺受体参与乙醇产生的不同作用，例如运动不协调或抗焦虑、催眠和强化作用。不同大脑区域的腺苷和多巴胺受体之间的共定位和相互作用也已得到充分记录。然而，很少有研究证明这些机制参与乙醇诱导的耐受性。目的：本研究的目的是评估腺苷和多巴胺受体在小鼠对乙醇引起的运动不协调的快速耐受性发展中的作用。方法：与旋转棒装置相关，急性施用腺苷受体拮抗剂咖啡因（非选择性）、8-环戊基-1,3-二丙基黄嘌呤（DPCPX，腺苷A，受体拮抗剂）和4-(2-[7-氨基-2-{2-呋喃基} {1,2,4}三唑-{2,3-a})的效果{1,3,5}三嗪-5-基氨基]乙基）苯酚（ZM241385，腺苷 A(2A) 受体拮抗剂），以及 R(+)-7-cloro-8-hidroxi-3-metil-1-fenil-2,3,4,5-tetrahidro-1H-3-benzazepine（SCH23390，多巴胺 D-1 受体拮抗剂）和舒必利（多巴胺 D-2 受体拮抗剂）单独或与乙醇（2.25 g/kg，腹膜内注射）组合进行了研究。二十四小时后，所有动物在接受相同剂量的乙醇后在旋转棒上重新进行测试。结果：重复施用乙醇促进第 2 天运动障碍的显着减少（即快速耐受）。这种作用可被咖啡因（3.0-30.0 mg/kg，腹腔注射）、DPCPX（3.0-6.0 mg/kg，腹腔注射）或 SCH23390（0.01-0.03 mg/kg，皮下注射）阻断，但不能被 ZM241385（0.5-1.0 mg/kg，腹腔注射）或舒必利阻断。 （1.0-3.0 毫克/千克，腹腔注射）。结论：我们的结果表明，小鼠对乙醇引起的运动障碍的快速耐受可能受到腺苷 A(1) 受体和多巴胺 D-1 受体的调节。
Rationale: Several reports have suggested the involvement of brain adenosine and dopamine receptors in different actions produced by ethanol such as motor incoordination or anxiolytic, hypnotic and reinforcing effects. The co-localization and interaction between adenosine and dopamine receptors in different brain regions has also been well documented. However, few studies have demonstrated the involvement of these mechanisms in the tolerance induced by ethanol. Objectives: The aim of the present study was to evaluate the role of adenosine and dopamine receptors in the development of rapid tolerance to ethanol-induced motor incoordination in mice. Methods: In connection with the rota-rod apparatus, the effects of acute administration of the adenosine receptor antagonists caffeine (non-selective), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, adenosine A, receptor antagonist) and 4-(2-[7-amino-2-{2-furyl} {1,2,4}triazolo-{2,3-a} {1,3,5}triazin-5-ylamino]ethyl)phenol (ZM241385, adenosine A(2A) receptor antagonist), together with R(+)-7-cloro-8-hidroxi-3-metil-1-fenil-2,3,4,5-tetrahidro-1H-3-benzazepine (SCH23390, dopamine D-1 receptor antagonist) and sulpiride (dopamine D-2 receptor antagonist), alone or in combination with ethanol (2.25 g/kg, i.p.), were studied. Twenty-four hours after, all animals were re-tested on the rota-rod after receiving the same dose of ethanol. Results: The repeated administration of ethanol promoted a significant reduction of motor impairment on day 2 (i.e. rapid tolerance). This effect was blocked by caffeine (3.0-30.0 mg/kg, i.p.), DPCPX (3.0-6.0 mg/kg, i.p.) or SCH23390 (0.01-0.03 mg/kg, s.c.), but not with ZM241385 (0.5-1.0 mg/kg, i.p.) or sulpiride (1.0-3.0 mg/kg, i.p.). Conclusions: Our results suggest that the rapid tolerance to ethanol-induced motor impairment in mice may be modulated by adenosine A(1) receptors and dopamine D-1 receptors.