6-hydroxydopamine treatments enhance behavioral responses to intracerebral microinjection of D1- and D2-dopamine agonists into nucleus accumbens and striatum without changing dopamine antagonist binding.
6-hydroxydopamine treatments enhance behavioral responses to intracerebral microinjection of D1- and D2-dopamine agonists into nucleus accumbens and striatum without changing dopamine antagonist binding.
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发表时间：
1987
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通讯作者：
G. Breese;G. Duncan;T. Napier;S. Bondy;L. Iorio;R. Mueller
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作者：
G. Breese;G. Duncan;T. Napier;S. Bondy;L. Iorio;R. Mueller
行为反应D1和D2-多巴胺激动剂增强时，这些激动剂全身给药6-羟基多巴胺（6-OHDA）损伤的大鼠。在本研究中，将SKF-38393（一种D1-多巴胺激动剂）微量注射到6-OHDA损伤新生大鼠的延髓核中，与对照组相比，运动活动明显增强，并产生剂量相关性增加。LY-171555，一种D2-激动剂，在该部位微量注射后，引起的自发活动比SKF-38393少。SKF-38393或LY-171555进入丘脑核给药，在给药于病变动物的剂量下，未增加病变大鼠的运动。在6-OHDA损伤的成年大鼠中，将SKF-38393微量注射到延髓核中也比LY-171555更能增加运动。如前所述，全身给予SKF-38393在成年6-OHDA损伤大鼠中几乎没有产生运动，而LY-171555产生了明显增强的反应。SKF-38393或LY-171555给药至6-OHDA损伤大鼠的尾状核，产生的运动活动可忽略不计，但确实诱导了与这些药物全身治疗后观察到的行为相似的刻板行为。刻板行为发生在更大程度上在6-OHDA损伤的大鼠比未损伤的控制。观察到多巴胺受体激动剂给药诱导的某些行为的区域特异性。尽管向6-OHDA损伤大鼠脑内微量注射D1和D2-多巴胺激动剂后，其行为反应增强，但[3 H]螺哌隆（D2-受体拮抗剂配体）和[3 H]SCH 23390（D1-受体拮抗剂配体）与纹状体和丘脑核组织的结合未发生显著变化。与6-OHDA损伤大鼠结合特征缺乏变化相反，氟哌啶醇治疗阻断多巴胺能传递引起纹状体中[3 H]螺哌隆结合位点升高，而不影响该位点的亲和力。然而，长期氟哌啶醇给药未显著改变[3 H]SCH 23390与纹状体膜的结合。这些发现表明，慢性多巴胺受体阻滞剂不需要产生与破坏含多巴胺神经元相同的适应机制。因此，通过多巴胺拮抗剂结合测定的受体特征的变化不能解释给药后D1-和D2-多巴胺受体激动剂给药至经麻醉或成年6-OHDA处理的大鼠后观察到的行为超敏性。
Behavioral responses to D1 and D2-dopamine agonists are enhanced when these agonists are administered systemically to 6-hydroxydopamine (6-OHDA)-lesioned rats. In the present investigation, microinjection of SKF-38393, a D1-dopamine agonist, into the nucleus accumbens of adult rats lesioned as neonates with 6-OHDA produced a dose-related increase in locomotor activity that was enhanced markedly compared to control. LY-171555, a D2-agonist, elicited less locomotor activity than did SKF-38393 after microinjection into this site. Administration of SKF-38393 or LY-171555 into the nucleus accumbens did not increase locomotion in unlesioned rats at the doses administered to lesioned animals. In adult-6-OHDA-lesioned rats, microinjection of SKF-38393 into the nucleus accumbens also increased locomotion more than did LY-171555. As described previously, systemic administration of SKF-38393 produced little locomotion in adult-6-OHDA-lesioned rats, whereas LY-171555 produced a markedly enhanced response. Administration of SKF-38393 or LY-171555 into the caudate nucleus of neonatally and adult-6-OHDA-lesioned rats produced negligible locomotor activity, but did induce stereotypic behaviors similar to those observed after systemic treatment with these drugs. Stereotypic behaviors occurred to a greater degree in the 6-OHDA-lesioned rats than in unlesioned controls. A regional specificity for certain behaviors induced by dopamine agonist administration was observed. In spite of the enhanced behavioral responses of D1 and D2-dopamine agonists after microinjection into the brain of 6-OHDA-lesioned rats, binding of [3H]spiperone (D2-receptor antagonist ligand) and [3H]SCH 23390 (D1-receptor antagonist ligand) to tissue from striatum and nucleus accumbens was not altered significantly. In contrast to this lack of change in binding characteristics in 6-OHDA-lesioned rats, blockade of dopaminergic transmission with haloperidol treatment caused an elevation of [3H]spiperone binding sites in striatum without affecting affinity for the site. However, chronic haloperidol treatment did not alter significantly [3H]SCH 23390 binding to striatal membranes. These latter findings suggest that chronic dopamine receptor blockade need not produce the same adaptive mechanisms as destruction of dopamine-containing neurons. Thus, a change in receptor characteristics as measured by dopamine antagonist binding does not account for the behavioral supersensitivity observed after D1- and D2-dopamine agonist administration to neonatally or adult-6-OHDA-treated rats.