GABAergic involvement in motor effects of an adenosine A2A receptor agonist in mice
GABAergic involvement in motor effects of an adenosine A2A receptor agonist in mice
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DOI：
10.1016/s0028-3908(99)00187-2
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Abraham, E
中科院分区：
文献类型：
--
作者：
Khisti, RT;Chopde, CT;Abraham, E
已知腺苷A（2A）激动剂可诱导猝睡并抑制多巴胺介导的运动亢进。腺苷A（2A）和多巴胺D-2受体之间的拮抗相互作用可调节纹状体神经元中gaba介导的神经传递。刺激腺苷A（2A）和多巴胺D-2受体分别增加和抑制苍白质GABA能神经元中GABA的释放。然而，gaba能神经传递在腺苷A（2A）受体运动效应中的作用尚不清楚。因此，在本研究中，gaba能药物对腺苷A（2A）受体激动剂（NECA-或CGS 21680）诱导的猝厥和抑制安非他明引起的运动亢进的影响进行了研究。预处理GABA， GABA(A)激动剂muscimol或GABA(B)激动剂巴氯芬增强，而GABA(A)拮抗剂双库兰减弱NECA-或CGS 21680诱导的猝厥。而GABA(B)拮抗剂苯氯酚和氨基戊酸对GABA(B)无明显影响。给药NECA或CGS 21680不仅能减少自发运动活动，还能拮抗安非他明引起的运动亢进。GABA或muscimol可增强NECA和CGS 21680的这些作用，而二胡兰可拮抗这些作用。这些发现为GABA在腺苷A（2A）受体激动剂的运动效应中的作用提供了行为学证据。腺苷A（2A）受体的激活增加GABA的释放，从而降低多巴胺能张力，诱导猝睡或抑制安非他明介导的运动亢进。(C) 2000 Elsevier Science Ltd.版权所有。
Adenosine A(2A) agonists are known to induce catalepsy and inhibit dopamine mediated motor hyperactivity, An antagonistic interaction between adenosine A(2A) and dopamine D-2 receptors is known to regulate GABA-mediated neurotransmission in striatopallidal neurons. Stimulation of adenosine A(2A) and dopamine D-2 receptors has been shown to increase and inhibit GABA release respectively in pallidal GABAergic neurons. However, the role of GABAergic neurotransmission in the motor effects of adenosine A(2A) receptors is not yet known. Therefore in the present study the effect of GABAergic agents on adenosine A(2A) receptor agonist (NECA- or CGS 21680) induced catalepsy and inhibition of amphetamine elicited motor hyperactivity was examined. Pretreatment with GABA, the GABA(A) agonist muscimol or the GABA(B) agonist baclofen potentiated whereas the GABA(A) antagonist bicuculline attenuated NECA- or CGS 21680-induced catalepsy. However, the GABA(B) antagonists phaclophen and delta-aminovaleric acid had no effect.. Administration of NECA or CGS 21680 not only reduced spontaneous locomotor activity but also antagonized amphetamine elicited motor hyperactivity. These effects of NECA and CGS 21680 were potentiated by GABA or muscimol and antagonized by bicuculline. These findings provide behavioral evidence for the role of GABA in the motor effects of adenosine A(2A) receptor agonists. Activation of adenosine A(2A) receptors increases GABA release which could reduce dopaminergic tone and induce catalepsy or inhibit amphetamine mediated motor hyperactivity. (C) 2000 Elsevier Science Ltd. All rights reserved.