Effects of acute administration of the GABA(B) receptor agonist baclofen on behavioral flexibility in rats.
Effects of acute administration of the GABA(B) receptor agonist baclofen on behavioral flexibility in rats.
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DOI：
10.1007/s00213-016-4321-y
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Bizon JL
中科院分区：
文献类型：
--
作者：
Beas BS;Setlow B;Bizon JL
面对环境变化时调整反应策略的能力对于正常的适应行为至关重要。这种行为灵活性受到皮质GABA能信号传导的实验性破坏以及以皮质过度兴奋为特征的精神分裂症和正常衰老等病症的损害。目前的研究旨在确定使用GABA（B）受体激动剂巴氯芬刺激GABA能信号传导是否可以促进行为灵活性。雄性Fischer 344大鼠接受了一项设置转换任务的训练，在该任务中，它们学会了区分两种反应杠杆以获得食物奖励。根据两个不同的响应规则发出正确的杠杆信号（规则1：通过提示灯发出正确的杠杆信号;规则2：通过其左/右位置发出正确的杠杆信号）。规则呈现的顺序各不相同，但它们总是按顺序呈现的，与试验和错误，以达到标准性能的第二个（集转移）规则提供的措施的行为灵活性。实验确定了GABA（B）受体激动剂巴氯芬（i. p.，0、1.0、2.5和4.0 mg/kg）。巴氯芬增强了移集性能。控制实验表明，这种增强不仅是由于改善的歧视学习，也不是由于受损的回忆的初始歧视规则。结果表明，巴氯芬可以促进行为的灵活性，这表明GABA（B）受体激动剂可能具有治疗神经精神疾病的行为功能障碍的效用。
The ability to adjust response strategies when faced with changes in the environment is critical for normal adaptive behavior. Such behavioral flexibility is compromised by experimental disruption of cortical GABAergic signaling, as well as in conditions such as schizophrenia and normal aging that are characterized by cortical hyperexcitability. The current studies were designed to determine whether stimulation of GABAergic signaling using the GABA(B) receptor agonist baclofen can facilitate behavioral flexibility. Male Fischer 344 rats were trained in a set-shifting task in which they learned to discriminate between two response levers to obtain a food reward. Correct levers were signaled in accordance with two distinct response rules (Rule 1: correct lever signaled by a cue light; Rule 2: correct lever signaled by its left/right position). The order of rule presentation varied, but they were always presented sequentially, with the trials and errors to reach criterion performance on the second (set shift) rule providing the measure of behavioral flexibility. Experiments determined the effects of the GABA(B) receptor agonist baclofen (i.p., 0, 1.0, 2.5 and 4.0 mg/kg) administered acutely before the shift to the second rule. Baclofen enhanced set-shifting performance. Control experiments demonstrated that this enhancement was not simply due to improved discrimination learning, nor was it due to impaired recall of the initial discrimination rule. The results demonstrate that baclofen can facilitate behavioral flexibility, suggesting that GABA(B) receptor agonists may have utility for treating behavioral dysfunction in neuropsychiatric disorders.