Brown F, Campbell W, Mitchell P J, Randall K
Br J Pharmacol. 1985 Apr;84(4):853-60. doi: 10.1111/j.1476-5381.1985.tb17379.x.
Criteria for distinguishing dopamine autoreceptor agonism from other mechanisms of inhibiting locomotion were examined, together with the relationship between inhibition of locomotion and dopamine synthesis. ED50 potencies to inhibit locomotion of mice were established for drugs from a number of categories. Spiperone 0.02 mg kg-1 significantly (P less than 0.05) reversed inhibition of locomotion by known dopamine agonists but not that by the other types of drug. Idazoxan antagonized inhibition of locomotion due to alpha 2-agonists but not dopamine agonists. RU 24926 (N-propyl-N,N-di[2-(3-hydroxyphenyl)ethyl]amine) was antagonized by both spiperone and idazoxan. Only for dopamine agonists was there good correlation (r = 0.97) between potencies to inhibit locomotion in mice and L-dihydroxyphenylalanine (L-DOPA) accumulation in the nucleus accumbens of rats treated with gamma-butyrolactone and 3-hydroxybenzylhydrazine. The specific dopamine D1-agonist, SK&F 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine), was inactive in both tests at doses up to 10 mg kg-1. The mixed dopamine agonist/antagonist, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine, commonly known as (-)-3-PPP, acted as a dopamine agonist in both tests but inhibited locomotion more potently than L-DOPA accumulation. The inhibitory effects of dopamine agonists on locomotion were not prevented by alpha-methyl-p-tyrosine pretreatment. The data suggest that spiperone-reversible inhibition of locomotion in mice is a good criterion for dopamine autoreceptor agonists. The receptors involved are affected by low doses of both dopamine agonists and antagonists and seem similar to those involved in the autoreceptor mediated inhibition of dopamine synthesis. However, inhibition of locomotion is not due simply to suppression of dopamine release brought about as a secondary consequence of effects on synthesis; a separate mechanism for inhibiting dopamine release is probably involved.
研究了区分多巴胺自身受体激动作用与其他抑制运动机制的标准，以及运动抑制与多巴胺合成之间的关系。确定了多种类别药物抑制小鼠运动的半数有效剂量（ED50）效力。0.02mg/kg的螺哌隆显著（P<0.05）逆转了已知多巴胺激动剂对运动的抑制作用，但对其他类型药物所致的运动抑制无此作用。育亨宾拮抗α2激动剂所致的运动抑制，但不拮抗多巴胺激动剂所致的运动抑制。RU 24926（N-丙基-N，N-二[2-（3-羟基苯基）乙基]胺）被螺哌隆和育亨宾均拮抗。仅对于多巴胺激动剂，在γ-丁内酯和3-羟基苄基肼处理的大鼠伏隔核中，抑制小鼠运动的效力与L-二羟基苯丙氨酸（L-DOPA）积累之间存在良好的相关性（r = 0.97）。特异性多巴胺D1激动剂SK&F 38393（2,3,4,5-四氢-7,8-二羟基-1-苯基-1H-3-苯并氮杂卓）在高达10mg/kg的剂量下在两项试验中均无活性。混合多巴胺激动剂/拮抗剂（-）-3-（3-羟基苯基）-N-丙基哌啶，通常称为（-）-3-PPP，在两项试验中均表现为多巴胺激动剂，但比L-DOPA积累更有效地抑制运动。α-甲基-p-酪氨酸预处理不能阻止多巴胺激动剂对运动的抑制作用。数据表明，螺哌隆可逆性抑制小鼠运动是多巴胺自身受体激动剂的良好标准。所涉及的受体受到低剂量多巴胺激动剂和拮抗剂的影响，似乎与自身受体介导的多巴胺合成抑制所涉及的受体相似。然而，运动抑制并非仅仅由于对合成的影响作为次要后果而导致的多巴胺释放抑制；可能涉及一种独立的抑制多巴胺释放的机制。
