THE ROLE OF D1 AND D2 DOPAMINE-RECEPTORS IN ORAL STEREOTYPY INDUCED BY DOPAMINERGIC STIMULATION OF THE VENTROLATERAL STRIATUM
THE ROLE OF D1 AND D2 DOPAMINE-RECEPTORS IN ORAL STEREOTYPY INDUCED BY DOPAMINERGIC STIMULATION OF THE VENTROLATERAL STRIATUM
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DOI：
10.1016/0306-4522(90)90221-o
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发表时间：
1990-01-01
期刊：
影响因子：
3.3
通讯作者：
KELLEY, AE
中科院分区：
文献类型：
--
作者：
DELFS, JM;KELLEY, AE
将苯丙胺微量注射到纹状体腹外侧区，会在大鼠中产生强迫性和强烈的口头刻板印象。虽然已知这些刻板行为是纹状体多巴胺神经元过度刺激的直接结果，但D1和D2受体在口腔刻板印象中的相对作用尚不清楚。据报道，在30分钟的测试期间，向腹外侧纹状体微量注射选择性D1激动剂SKF 38393(0，0.3，3.0，30.0ug，0.5µl)，没有引起明显的行为变化。然而，观察到在注射后3-4h出现强烈的自咬现象。对这些动物的组织学检查显示出广泛的组织损伤，咬伤的延迟发生被推测是由SKF 38393的神经毒性作用造成的。奎比罗(0，0.3，3.0，30.0.MU.一种选择性的D2激动剂)，导致口腔面部行为的剂量依赖性增加，如舔、吃木片、低头、嗅闻和嘴部运动。在使用喹比罗治疗后，没有观察到强烈的口腔刻板印象，如咬或咬。将混合激动剂多巴胺(0，2.0，10.0，20.0微克，0.5微升)注入腹侧纹状体可引起强烈的口述刻板印象。这种行为几乎完全是自咬行为，类似于向该区域微量注射苯丙胺后观察到的行为。当全身注射氟哌啶醇(0.2 mg/kg)或腹外侧纹状体内注射(2.5微克/0.5微升)时，可有效地阻断由纹状体腹外侧区微量注射苯丙胺引起的口述刻板印象。预先给予D1拮抗剂SCH 23390(0，0.01，0.1 mg/kg，i.p.)D2拮抗剂拉氯必利(0，0.05，0.50，1.0 mg/kg，i.p.)以剂量依赖的方式对抗安非他明诱导的口腔刻板印象。这些发现表明，在与口腔行为有关的纹状体部位，同时刺激两种受体亚型对于表达强烈的口腔刻板印象是必要的。
Microinjection of amphetamine into the ventrolateral region of the striatum results in compulsive and intense oral stereotypes in the rat. Although these stereotyped behaviors are known to be a direct result of excessive stimulation of the striatal dopamine neurons, the relative roles of the D1 and D2 receptors in oral stereotypies are not clearly understood. It is reported here that microinjection of the selective D1 agonist, SKF 38393 (0, 0.3, 3.0, 30.0 .mu.g in 0.5 .mu.l vehicle) into the ventrolateral striatum resulted in no observable changes in behavior during the 30-min test period. However, it was observed that intense self-biting emerged 3-4 h following injection. Examination of histology from these animals revealed extensive tissue damage and the delayed onset of biting was hypothesized to result from a neurotoxic effect of SKF 38393. Infusion of quinpirole (0, 0.3, 3.0, 30.0 .mu. g in 0.5 .mu.l vehicle), a selective D2 agonist, resulted in a dose-dependent increase in orofacial behaviors such as licking, wood-chip eating, head-down, sniffing and mouth movements. Intense oral stereotypies such as biting or gnawning were not observed following treatment with quinpirole. Infusion of the mixed agonist dopamine (0, 2.0, 10.0, 20.0 .mu.g in 0.5 .mu.l vehicle) into the ventrolateal striatum was found to elicit intense oral stereotypy. This behavior consisted almost exclusively of self-biting similar to that observed following amphetamine microinjection into this region. Haloperidol, when given a either a systemic (0.2 mg/kg) or intra-ventrolateral striatum (2.5 .mu.g/0.5 .mu.l) pretreatment, effectively blocked oral stereotypies induced by amphetamine microinjection into the ventrolateral striatum. Pretreatment with either the D1 antagonist SCH 23390 (0, 0.01, 0.1 mg/kg, i.p.) or the D2 antagonist raclopride (0, 0.05, 0.50, 1.0 mg/kg, i.p.) antagonized amphetamine-induced oral stereotypy in a dose-dependent manner. These findings demonstrate that within the striatal site specifically implicated in oral behavior, concurrent stimulation of both receptor subtypes is necessary for the expression of intense oral stereotypies.