Bantick R Alexander, De Vries Michiel H, Grasby Paul M
Cyclotron Unit, CSC, The Hammersmith Hospital, Imperial College London, London W12 0NN, United Kingdom.
Synapse. 2005 Aug;57(2):67-75. doi: 10.1002/syn.20156.
5-HT1A receptor agonists consistently reduce neuroleptic induced catalepsy in rats. A serotonin-dopamine interaction has been proposed to underlie this effect. Specifically, 5-HT1A receptor agonists may reduce the activity of serotonergic projections that inhibit dopaminergic nigrostriatal neurones, therefore increasing dorsal striatal dopamine levels and partially overcoming the neuroleptic blockade of D2 receptors. We tested the hypothesis that 5-HT1A receptor agonists increase striatal dopamine release in man using PET scanning with the selective D2 receptor radioligand [11C]raclopride, which is sensitive to endogenous dopamine levels. Six healthy volunteers received two PET scans, one after placebo, the other after 1 mg flesinoxan, a selective 5-HT1A receptor agonist. Binding potential values for striatal subdivisions were determined using a simplified reference tissue model. We did not find any difference in striatal [11C]raclopride binding between conditions, even though flesinoxan lead to typical 5-HT1A receptor agonist side effects and produced elevation of growth hormone in five of the six subjects. Our results suggest that the anticataleptic effect of 5-HT1A receptor agonists is not mediated by striatal dopamine release, and indicates a need for further research with other suitable 5-HT1A receptor agonists.
5-羟色胺1A（5-HT1A）受体激动剂始终能减轻大鼠中由抗精神病药物引起的僵住症。有人提出5-羟色胺-多巴胺相互作用是这一效应的基础。具体而言，5-HT1A受体激动剂可能会降低抑制多巴胺能黑质纹状体神经元的5-羟色胺能投射的活性，从而提高背侧纹状体多巴胺水平，并部分克服抗精神病药物对D2受体的阻滞作用。我们使用对内源性多巴胺水平敏感的选择性D2受体放射性配体[11C]雷氯必利进行正电子发射断层扫描（PET），以检验5-HT1A受体激动剂是否会增加人体纹状体多巴胺释放这一假设。六名健康志愿者接受了两次PET扫描，一次在服用安慰剂后，另一次在服用1毫克选择性5-HT1A受体激动剂氟司必林后。使用简化参考组织模型确定纹状体各亚区的结合潜能值。尽管氟司必林导致了典型的5-HT1A受体激动剂副作用，并且在六名受试者中的五名中引起了生长激素升高，但我们并未发现不同条件下纹状体[11C]雷氯必利结合存在任何差异。我们的结果表明，5-HT1A受体激动剂的抗僵住症作用不是由纹状体多巴胺释放介导的，这表明需要使用其他合适的5-HT1A受体激动剂进行进一步研究。
