Changes in G‐protein activity mediated through the stimulation of dopamine and GABA B receptors in the mesolimbic dopaminergic system of morphine‐sensitized mice
Changes in G‐protein activity mediated through the stimulation of dopamine and GABA B receptors in the mesolimbic dopaminergic system of morphine‐sensitized mice
复制标题
DOI：
10.1080/13556210310001602239
复制
发表时间：
2003-09
影响因子：
3.4
通讯作者：
M. Narita;M. Shibasaki;K. Mizuo;Tsutomu Suzuki
中科院分区：
文献类型：
--
作者：
M. Narita;M. Shibasaki;K. Mizuo;Tsutomu Suzuki
行为敏化被认为是反复滥用药物后行为反应的增加和大脑功能的不良长期变化。我们研究了间歇性吗啡治疗引起的对过度运动的行为敏感性是否可能是由于多巴胺和 GABA B 受体激活小鼠大脑奖励系统中 G 蛋白的功能发生变化所致。间歇性吗啡治疗会导致小鼠边缘前脑中多巴胺受体调节的 G 蛋白激活上调，而这种治疗会导致 GABA B 受体功能下调，从而激活小鼠下中脑中的 G 蛋白。在行为实验中，间歇性给予吗啡与多巴胺受体拮抗剂氟哌啶醇或 GABA B 受体激动剂巴氯芬联用可消除吗啡引起的过度运动过敏的发展。目前的数据提供的证据表明，这些 G 蛋白激活变化可能导致小鼠对吗啡诱导的过度运动行为敏感。
The behavioural sensitization has been recognized as the increased behavioural response and the undesirable long‐lasting changes in brain functions after repeated administration of abuse drugs. We examined whether behavioural sensitization to hyperlocomotion induced by intermittent morphine treatment could result from any changes in dopamine and GABA B receptor functions to activate G‐proteins in the brain rewarding system in mice. Intermittent morphine treatment results in the upregulation of dopamine receptor‐regulated G‐protein activation in the mouse limbic forebrain, whereas this treatment causes the downregulation of GABA B receptor function to activate G‐protein in the mouse lower midbrain. In behavioural experiments, intermittent administration of morphine in combination with either a dopamine receptor antagonist haloperidol or a GABA B receptor agonist baclofen abolished the development of sensitization to morphine‐induced hyperlocomotion. The present data provide evidence that these G‐protein activation changes may lead to behavioural sensitization to morphine‐induced hyperlocomotion in mice.