Subsensitivity to dopaminergic drugs in periadolescent rats: a behavioral and neurochemical analysis
Subsensitivity to dopaminergic drugs in periadolescent rats: a behavioral and neurochemical analysis
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DOI：
10.1016/s0165-3806(98)00116-3
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发表时间：
1998-11-01
期刊：
影响因子：
--
通讯作者：
Jackson, D
中科院分区：
文献类型：
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作者：
Bolanos, CA;Glatt, SJ;Jackson, D
据报道，出生后30-40天（PD）的大鼠与年轻或年老的大鼠相比，对多巴胺能药物的行为效应的反应不同。本研究观察了苯丙胺（AMPH）对大鼠运动行为的影响以及多巴胺能药物对大鼠纹状体乙酰胆碱（ACh）释放的影响。AMPH增加多巴胺（DA）介导的运动行为（自发活动和刻板）在青春期和成年大鼠，然而，这些反应是在青春期大鼠的幅度较小。在成年大鼠中，可卡因和诺米芬辛抑制ACh溢出的剂量依赖性的方式。在青春期大鼠，乙酰胆碱溢出最大限度地抑制在较低的药物浓度（5 μ M）比在成年大鼠（10 μ M），这意味着在这些大鼠的敏感性增加。阿扑吗啡抑制乙酰胆碱溢出的剂量依赖性的方式在切片从成年大鼠。与此相反，阿扑吗啡并没有一贯抑制乙酰胆碱溢出的纹状体切片制备的青春期大鼠。总的来说，这项研究的结果表明，行为的不敏感性，在围青春期大鼠的AMPH。DA再摄取阻滞剂对纹状体胆碱能神经元DA调制的影响的检查未能揭示相应的次敏感性。事实上，ACh的释放是更敏感的DA再摄取阻滞剂在青春期大鼠。后者的发现表明，未公开的因素推翻多巴胺能调制纹状体神经元的行为在青春期大鼠的调解。我们建议，在围青春期，DA传输是短暂的升高。这导致胆碱能受体的突触后超敏性，并因此在用多巴胺能药物激发时诱导行为亚敏感性。增加胆碱能张力可能介导行为的亚敏感性，尽管药物诱导的DA升高。（C）1998年爱思唯尔科学B. V.保留所有权利。
It has been reported that post-natal day (PD) 30-40 rats respond differently to the behavioral effects of dopaminergic drugs when compared to younger or older rats. In this study, the behavioral effects of amphetamine (AMPH) on motor behavior and the effects of dopaminergic drugs on striatal acelylcholine (ACh) release were evaluated in periadolescent (PD35) and adult rats. AMPH increased dopamine (DA)-mediated motor behaviors (locomotor activity and stereotypy) in periadolescent and adult rats; however, these responses were of a lesser magnitude in periadolescent rats. In adult rats, cocaine and nomifensine inhibited ACh overflow in a dose-dependent manner. In periadolescent rats, ACh overflow was maximally inhibited at a lower drug concentration (5 mu M) than in adult rats (10 mu M) signifying increased sensitivity in these rats. Apomorphine inhibited ACh overflow in a dose-dependent fashion in slices from adult rats. In contrast, apomorphine did not consistently inhibit ACh overflow in striatal slices prepared from periadolescent rats. Collectively, the results of this study demonstrate behavioral subsensitivity to AMPH in periadolescent rats. Examination of the effects of DA reuptake blockers on DA modulation of striatal cholinergic neurons failed to reveal a corresponding subsensitivity. In fact, ACh release was more sensitive to DA reuptake blockers in periadolescent rats. This latter finding suggests that undisclosed factors override dopaminergic modulation of striatal neurons in the mediation of behavior in periadolescent rats. We propose that during periadolescence, DA transmission is transiently elevated. This results in post-synaptic supersensitivity of cholinergic receptors and consequently induces behavioral subsensitivity when challenged with dopaminergic drugs. Increased cholinergic tone may mediate behavioral subsensitivity despite drug-induced elevations in DA. (C) 1998 Elsevier Science B.V. All rights reserved.