Importance of D1 and D2 receptors in the dorsal caudate-putamen for the locomotor activity and stereotyped behaviors of preweanling rats.

Importance of D1 and D2 receptors in the dorsal caudate-putamen for the locomotor activity and stereotyped behaviors of preweanling rats.
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DOI:
10.1016/j.neuroscience.2011.03.037
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发表时间:
2011-06-02
期刊:
影响因子:
3.3
通讯作者:
McDougall SA
McDougall SA
中科院分区:
医学3区
文献类型:
--
作者:
Charntikov S;Der-Ghazarian T;Herbert MS;Horn LR;Widarma CB;Gutierrez A;Varela FA;McDougall SA

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多巴胺能化合物经常影响未习得的行为的断奶前和成年大鼠不同,虽然这些年龄依赖性的行为影响的大脑区域尚未被指定。一个候选的大脑区域是背侧尾壳核(CPU),因此,本研究的目标是确定是否D1和D2受体在背侧CPU能够调制未学习的行为断奶前大鼠。在实验1和2中,选择性和非选择性多巴胺受体激动剂双侧微量注射到背侧CPU出生后第18天(PD)和自发活动和刻板性进行了测量。在实验3中,通过单独或组合显微注射D1激动剂SKF-82958和D2/D3激动剂昆吡罗来评估D1和D2受体的功能偶联。在实验4和5中,将喹吡罗和D1受体拮抗剂SCH-23390,或SKF-82958和D2受体拮抗剂雷氯必利共同给予背侧CPu,以进一步评估功能性D1或D2受体系统是否是喹吡罗或SKF-82958诱导行为表达所必需的。结果表明,选择性刺激背侧CPu的D_1或D_2受体,可增加断奶前大鼠的自主活动和刻板行为。受体偶联在PD 18上是明显的,因为联合给予阈下剂量的SKF-82958和喹吡罗比单独给予任一种激动剂产生更多的运动活性。最后,多巴胺拮抗剂实验表明,D1和D2受体系统必须对SKF-82958或喹吡罗诱导的运动活性起作用,才能完全表现出来。当目前的数据进行比较,从非个体发育研究的结果,它似乎是在背侧CPU的D1和D2受体的药理学操作影响行为的断奶前和成年大鼠在一般相似的方式,虽然一些重要的年龄依赖性差异是显而易见的。例如,D1和/或D2激动剂优先诱导运动活动,而不是强烈的刻板,在年轻的动物。
Dopaminergic compounds often affect the unlearned behaviors of preweanling and adult rats differently, although the brain regions underlying these age-dependent behavioral effects have not been specified. A candidate brain region is the dorsal caudate-putamen (CPu); thus, a goal of the present study was to determine whether D1 and D2 receptors in the dorsal CPu are capable of modulating the unlearned behaviors of preweanling rats. In Experiments 1 and 2, selective and nonselective dopamine agonists were bilaterally microinjected into the dorsal CPu on postnatal day (PD) 18 and both locomotor activity and stereotypy were measured. In Experiment 3, the functional coupling of D1 and D2 receptors was assessed by microinjecting the D1 agonist SKF-82958 and the D2/D3 agonist quinpirole either alone or in combination. In Experiments 4 and 5, quinpirole and the D1 receptor antagonist SCH-23390, or SKF-82958 and the D2 receptor antagonist raclopride, were co-administered into the dorsal CPu to further assess whether a functional D1 or D2 receptor system is necessary for the expression of quinpirole- or SKF-82958-induced behaviors. Results showed that selective stimulation of D1 or D2 receptors in the dorsal CPu increased both the locomotor activity and stereotypy of preweanling rats. Receptor coupling was evident on PD 18 because co-administration of a subthreshold dose of SKF-82958 and quinpirole produced more locomotor activity than either agonist alone. Lastly, the dopamine antagonist experiments showed that both D1 and D2 receptor systems must be functional for SKF-82958- or quinpirole-induced locomotor activity to be fully manifested. When the present data are compared to results from non-ontogenetic studies, it appears that pharmacological manipulation of D1 and D2 receptors in the dorsal CPu affects the behavior of preweanling and adult rats in a generally similar manner, although some important age-dependent differences are apparent. For example, D1 and/or D2 agonists preferentially induce locomotor activity, and not intense stereotypy, in younger animals.
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发表时间: 2000-01-01
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