Evidence for genetically mediated dysfunction of the central dopaminergic system in the stargazer rat
Evidence for genetically mediated dysfunction of the central dopaminergic system in the stargazer rat
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DOI：
10.1007/bf02246178
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发表时间：
1996-01-01
影响因子：
3.4
通讯作者：
Ashby, CR
中科院分区：
文献类型：
--
作者：
Brock, JW;Ashby, CR
观星大鼠是一种常染色体隐性突变体（纯合 stg/stg），表现出异常行为，其特征是刻板的头部运动、转圈和高水平的行走活动。杂合子 (stg/+) 同窝小鼠表现出正常的自发行为。在这项研究中，使用喹吡罗和氟哌啶醇，比较了观星者及其未受影响的同窝动物对多巴胺 D-2/D-3 受体刺激和抑制的行为反应。据观察，观星者对 (-)-喹吡罗（50 μg/kg，IP）的反应比同窝动物打哈欠的次数明显更少。氟哌啶醇（HAL 0.1 mg/kg 和 0.3 mg/kg，SC）引起突变体定型头部运动的减少，这种减少具有时间和剂量依赖性。在正常同窝仔鼠中，HAL 会抑制运动活动，并以时间和剂量依赖性方式产生僵住症。在观星者中，两种剂量的 HAL 对运动活动的抑制程度与同窝小鼠相似。然而，在使用 0.1 mg/kg HAL 的突变体中未检测到僵直症。 0.3 mg/kg HAL 的剂量仅具有微弱的致死作用。总体而言，观星者表现出的一系列异常行为以及目前 D-2/D-3 受体不敏感的证据表明，观星者具有遗传介导的中枢多巴胺能系统功能障碍。
The stargazer rat is an autosomal recessive mutant (homozygous stg/stg) that displays abnormal behavior, characterized by stereotypic head-movement, circling, and a high level of ambulatory activity. Heterozygous (stg/+) littermates display normal spontaneous behaviors. In this study, stargazers and their unaffected littermates were compared in their behavioral responses to both stimulation and inhibition of dopamine D-2/D-3 receptors, using quinpirole and haloperidol. Stargazers were observed to yawn a significantly fewer number of times than littermates in response to (-)-quinpirole (50 mu g/kg, IP). Haloperidol (HAL 0.1 mg/kg and 0.3 mg/kg, SC) caused a decrease in stereotypic head movement in the mutants that was both time- and dose-dependent. In normal littermates, HAL inhibited locomotor activity and produced catalepsy in a time- and dose-dependent manner. In stargazers, both doses of HAL inhibited locomotor activity to a similar degree as in the littermates. However, no catalepsy was detectable in the mutants using 0.1 mg/kg of HAL. A dose of 0.3 mg/kg HAL was only weakly cataleptogenic. Overall, the spectrum of abnormal behaviors expressed by the stargazers and the present evidence of D-2/D-3 receptor subsensitivity suggest that stargazers possess a genetically mediated dysfunction of the central dopaminergic system.