Watanabe H, Hata S, Watanabe K
Nihon Yakurigaku Zasshi. 1983 Oct;82(4):247-57.
In order to elucidate pharmacological properties of rotational behaviour produced by unilateral electrical stimulation of the substantia nigra, effects of 6-hydroxydopamine treatment, dopamine receptor antagonists and agonists were investigated in the rat. Dopamine and its metabolites in the striatum were estimated after the stimulation. Intranigral treatment of 6-hydroxydopamine remarkably inhibited rotational behaviour induced by electrical stimulation. Antipsychotic drugs, 1 mg/kg haloperidol i.p. and 1 mg/kg pimozide i.p., decreased the behaviour by 50% of the control level. Sulpiride and metoclopramide did not exert significant influences on the behaviour. The dopamine receptor agonist apomorphine, 0.5 and 1 mg/kg s.c., markedly suppressed the stimulation-induced rotation, although it produced stereotypy, i.e. sniffing and gnawing. Bromocriptine, 10 mg/kg i.p., also suppressed rotational behaviour and produced locomotor activation without electrical stimulation. Methamphetamine did not have significant effects on the behaviour. Unilateral electrical stimulation of the substantia nigra produced an increase in the content of dopamine metabolites in the ipsilateral striatum of the rat pretreated with probenecid. These results suggest that the nigrostriatal dopaminergic system plays an important role in rotational behaviour produced by the electrical stimulation, and dopamine receptor agonists suppress the behaviour through a stimulating effect on the presynaptic dopamine receptor.
为了阐明单侧电刺激黑质所产生的旋转行为的药理学特性,研究了6-羟基多巴胺处理、多巴胺受体拮抗剂和激动剂对大鼠的影响。刺激后测定纹状体内的多巴胺及其代谢产物。黑质内注射6-羟基多巴胺可显著抑制电刺激诱导的旋转行为。抗精神病药物,腹腔注射1mg/kg氟哌啶醇和1mg/kg匹莫齐特,可使该行为降低至对照水平的50%。舒必利和甲氧氯普胺对该行为无显著影响。多巴胺受体激动剂阿扑吗啡,皮下注射0.5mg/kg和1mg/kg,虽会产生刻板行为,即嗅闻和啃咬,但能显著抑制刺激诱导的旋转。腹腔注射10mg/kg溴隐亭也可抑制旋转行为,并在无电刺激的情况下产生运动激活。甲基苯丙胺对该行为无显著影响。在预先用丙磺舒处理的大鼠中,单侧电刺激黑质可使同侧纹状体内多巴胺代谢产物的含量增加。这些结果表明,黑质纹状体多巴胺能系统在电刺激产生的旋转行为中起重要作用,多巴胺受体激动剂通过对突触前多巴胺受体的刺激作用来抑制该行为。