POSSIBLE ROLE OF STRIATAL ADENOSINE IN THE MODULATION OF ACUTE ETHANOL-INDUCED MOTOR INCOORDINATION IN RATS
POSSIBLE ROLE OF STRIATAL ADENOSINE IN THE MODULATION OF ACUTE ETHANOL-INDUCED MOTOR INCOORDINATION IN RATS
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DOI：
10.1111/j.1530-0277.1995.tb00964.x
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发表时间：
1995-08-01
影响因子：
3.2
通讯作者：
DAR, MS
中科院分区：
文献类型：
--
作者：
MENG, ZH;DAR, MS
我们实验室的一些报告表明，脑腺苷能系统参与了乙醇诱导的运动不协调(EIMI)。这项研究是先前工作的延伸，旨在评估纹状体腺苷在雄性SD大鼠EIMI中的作用。以1.5g/kg乙醇引起的运动不协调为测试反应，研究了乙醇与纹状体内腺苷激动剂和拮抗剂之间可能的行为相互作用。纹状体(IST)注射腺苷A(1)-、A(1)=A(2)-和A(2)-选择性激动剂R(-)N-6-(2-苯基异丙基)腺苷(R-PIA)、5‘-N-乙基氨基-腺苷(NECA)和5’-(N-环丙基)-氨基-腺苷(5‘-(N-环丙基)-氨基-腺苷)可显著增强EIMI，并呈剂量依赖性。正常的运动协调性没有显著变化，即使在腺苷激动剂的最高IST剂量之后是生理盐水而不是乙醇，这表明这些药物的行为相互作用对乙醇是选择性的。由于高密度腺苷受体的存在，以及高水平的腺苷，已知不参与正常运动功能的海马区被选为对照脑区。海马区NECA不能改变EIMI，提示纹状体而不是海马腺苷能系统在EIMI的调节中起特定作用。腺苷激动剂N-6-环己基腺苷(CHA)和CGS-21680对EIMI的增强作用分别被腺苷A(1)和A(2)选择性拮抗剂8-环戊基-1，3-二丙基黄嘌呤和3，7-二甲基-1-丙基黄嘌呤阻断，提示腺苷受体参与了这一功能相互作用。基于腺苷激动剂的排序效力，腺苷A(1)受体在EIMI的纹状体腺苷能调制中的作用受到青睐。用百日咳毒素(PT)而不是PTβ-低聚物预处理，几乎完全消除了CHA对EIMI的增强作用，进一步支持了腺苷A(1)受体在EIMI中的有利作用。组织学和IST[H-3]R-PIA分布数据证实，所观察到的行为效应是纹状体内微量注射药物的专属纹状体分布所致。数据表明，急性EIMI的调节机制是纹状体腺苷受体介导的机制(S)，以及这些腺苷受体与PT敏感的G(I)蛋白的偶联。
Several reports from our laboratory have suggested the involvement of the brain adenosinergic system in ethanol-induced motor incoordination (EIMI). This study is an extension of the previous work and pertains to the evaluation of the role of the striatal adenosine in EIMI in male Sprague-Dawley rats. Using the motor incoordination induced by 1.5 g/kg of ethanol (ip) as a test response, the possible behavioral interactions between ethanol and adenosine agonists and antagonists in the striatum were investigated. Intrastriatal (IST) administration of adenosine A(1)-, A(1) = A(2)-, and A(2)-selective agonists, R(-)N-6-(2-phenylisopropyl)adenosine (R-PIA), 5'-N-ethylcarboxamido-adenosine (NECA), and 5'-(N-cyclopropyl)-carboxamidoadenosine, respectively, significantly and dose-dependently accentuated EIMI when evaluated by rotorod test, suggesting the striatal adenosinergic modulation of EIMI. No significant change in normal motor coordination was noted, even when the highest IST doses of adenosine agonists were followed by saline instead of ethanol, suggesting that the observed behavioral interactions of these drugs were selective to ethanol. Hippocampus, which is known not to be involved in the normal motor functions, was selected as a control brain area because of the presence of high density of adenosine receptors, as well as the high levels of adenosine. Intrahippocampal NECA failed to alter EIMI, indicating the specific role of striatal and not hippocampal adenosinergic system in the modulation of EIMI. The potentiating effects of adenosine agonists N-6-cyclohexyladenosine (CHA) and CGS-21680 on EIMI were blocked by adenosine A(1)- and A(2)-selective antagonists, 8-cyclopentyl-1,3-dipropylxanthine and 3,7-dimethyl-1-propargylxanthine, respectively, suggesting the participation of specific adenosine receptors in this functional interaction. A role for the adenosine A(1) receptor in the striatal adenosinergic modulation of EIMI was favored based on the rank-order potency of adenosine agonists. IST pretreatment with pertussis toxin (PT), but not with PT beta-oligomer, nearly completely eliminated the accentuation of EIMI by CHA, further supporting the favored role of adenosine A(1) receptors in EIMI. Histological and IST [H-3]R-PIA distribution data confirmed that the observed behavioral effects were caused by exclusive striatal distribution of intrastriatally microinjected drugs. Data obtained suggested modulation of acute EIMI by striatal adenosine receptor-mediated mechanism(s) and the coupling of these adenosine receptors to the PT-sensitive G(i) protein.