Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul Avenida Ipiranga, Porto Alegre, RS, Brazil
Comp Biochem Physiol C Toxicol Pharmacol. 2009 Jul;150(1):10-5. doi: 10.1016/j.cbpc.2009.01.008.
Antipsychotic agents are widely used for the treatment of psychotic symptoms in patients with several brain disorders. Antipsychotic drugs principally affect dopamine systems with the newer ones also affecting serotonin, norepinephrine, and histamine systems. Other transmitter systems can be involved with selected antipsychotic drugs but effects on cholinergic system are less known. Considerable evidence has shown that complex interactions between dopaminergic and cholinergic systems are critical for the proper regulation of motor control and memory. These neurotransmitter systems have been studied in zebrafish, which has recently become a focus of neurobehavioral studies. Therefore, we have evaluated the in vitro and in vivo effects of sulpiride, olanzapine, and haloperidol on acetylcholinesterase activity and ache expression pattern in zebrafish brain. For in vitro studies, all drugs were able to promote a decrease on acetylcholinesterase activity. For in vivo studies, olanzapine and sulpiride exposure did not change acetylcholinesterase activity. In contrast, this enzyme activity was significantly increased at 5 and 9 microM haloperidol (29.9% and 20.4%, respectively). Haloperidol exposure was able to increase acetylcholinesterase mRNA transcripts. These findings have suggested that the alterations in zebrafish acetylcholinesterase could reveal molecular mechanisms related to cholinergic signaling induced by antipsychotic treatment.
抗精神病药物被广泛用于治疗多种脑部疾病患者的精神病症状。抗精神病药物主要影响多巴胺系统，而新型药物也影响 5-羟色胺、去甲肾上腺素和组胺系统。其他递质系统可能与某些抗精神病药物有关，但胆碱能系统的作用知之甚少。大量证据表明，多巴胺能和胆碱能系统之间的复杂相互作用对于运动控制和记忆的正常调节至关重要。这些神经递质系统在斑马鱼中得到了研究，斑马鱼最近已成为神经行为研究的焦点。因此，我们评估了舒必利、奥氮平和氟哌啶醇对斑马鱼大脑中乙酰胆碱酯酶活性和 ache 表达模式的体外和体内影响。在体外研究中，所有药物都能促进乙酰胆碱酯酶活性的降低。在体内研究中，奥氮平和舒必利暴露并没有改变乙酰胆碱酯酶的活性。相反，5 和 9 μM 氟哌啶醇（分别为 29.9%和 20.4%）能显著增加该酶的活性。氟哌啶醇暴露能增加乙酰胆碱酯酶 mRNA 转录本。这些发现表明，斑马鱼乙酰胆碱酯酶的改变可能揭示了与抗精神病药物治疗诱导的胆碱能信号相关的分子机制。
