Pranzatelli M R, Snodgrass S R
Brain Res. 1986 Jan 29;364(1):67-76. doi: 10.1016/0006-8993(86)90988-1.
This study evaluated the behavioral elements of three 5-HT-related syndromes (intraperitoneal 5-hydroxytryptophan after intracisternal 5,7-dihydroxytryptamine (DHT), p-chloroamphetamine (PCA), fenfluramine (FF), or combinations of drugs) scored from video-tapes and their relationship to locomotor activity (LMA) photocell recording, regional monoamine concentration and S-1 receptor binding. Rearing was eliminated by drugs which produce the myoclonic syndrome and was the single best indicator of control treatments (saline or 5-HTP in unlesioned rats and saline in DHT-lesioned rats). Global 'abnormality', hunching (rigid arching of back), hindlimb abduction, forepaw myoclonus, stereotyped lateral head movements, backing, and immobility occurred significantly only in drug-treated rats. Multiple forms of myoclonus (appendicular and truncal) and convulsions were dose-dependent drug effects. Both 5-HTP (after DHT) and PCA increased LMA significantly, but hyperactivity induced by PCA could be blocked by giving 5-HTP concomitantly. Substantial 5-HT presynaptic destruction by DHT prevented backing but not other behavioral or locomotor effects of FF and PCA. Drug combinations did not produce additive behavioral effects. Backing, immobility, and locomotor activity best differentiated between drug treatments, and could be used to correctly allocate animals to drug groups. Drug treatments also could be differentiated by reducing the number of behavioral variables into summary variables (principal components) and by discriminant analysis. Only forepaw myoclonus and total behavioral score were correlated with 5-HT concentrations (brainstem), indicating behavioral heterogeneity. Our study suggests that there is a common core 'myoclonic-serotonergic' syndrome (forepaw myoclonus, head weaving, hindlimb abduction, hunching) of stimulation of 5-HT receptors plus additional drug-specific elements (backing, LMA). Although brainstem receptors appear to be an important locus for some of these behaviors, S-1 receptors do not explain the behavioral supersensitivity to 5-HTP in our DHT-lesioned rats.
本研究评估了三种与5-羟色胺（5-HT）相关综合征（脑池内注射5,7-二羟色胺（DHT）后腹腔注射5-羟色氨酸、对氯苯丙胺（PCA）、芬氟拉明（FF）或药物组合）的行为要素，这些要素通过录像评分，以及它们与运动活性（LMA）光电记录、区域单胺浓度和S-1受体结合的关系。产生肌阵挛综合征的药物可消除竖毛行为，竖毛是对照处理（未损伤大鼠中的生理盐水或5-羟色氨酸，以及DHT损伤大鼠中的生理盐水）的唯一最佳指标。整体“异常”、弓背（背部僵硬拱起）、后肢外展、前爪肌阵挛、刻板的侧向头部运动、倒退和不动仅在药物处理的大鼠中显著出现。多种形式的肌阵挛（肢体和躯干）和惊厥是剂量依赖性的药物效应。5-羟色氨酸（DHT后）和PCA均显著增加LMA，但PCA诱导的多动可通过同时给予5-羟色氨酸来阻断。DHT对5-HT突触前的大量破坏可阻止倒退，但不能阻止FF和PCA的其他行为或运动效应。药物组合未产生相加的行为效应。倒退、不动和运动活性在药物处理之间的区分最佳，可用于将动物正确分配到药物组。通过将行为变量数量减少为汇总变量（主成分）并进行判别分析，也可区分药物处理。仅前爪肌阵挛和总行为评分与5-HT浓度（脑干）相关，表明行为存在异质性。我们的研究表明，存在一个共同的核心“肌阵挛-5-羟色胺能”综合征（前爪肌阵挛、头部摆动、后肢外展、弓背），这是5-HT受体刺激加上其他药物特异性要素（倒退、LMA）的结果。尽管脑干受体似乎是其中一些行为的重要位点，但S-1受体并不能解释我们的DHT损伤大鼠对5-羟色氨酸的行为超敏反应。
