Lian Jiamei, Pan Bo, Deng Chao
Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong 2522, NSW, Australia; School of Medicine, University of Wollongong, Wollongong 2522, NSW, Australia.
Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, Wollongong 2522, NSW, Australia; School of Medicine, University of Wollongong, Wollongong 2522, NSW, Australia.
Pharmacol Rep. 2016 Oct;68(5):1028-35. doi: 10.1016/j.pharep.2016.06.003. Epub 2016 Jul 17.
Antipsychotic drugs (APDs) were developed to treat schizophrenia in adults; however they have been increasingly prescribed (mostly "off-label") for children and adolescents. This study aimed to investigate the effects of aripiprazole, olanzapine and risperidone on the binding of serotonin (5-HT) and dopamine receptors in juvenile rat brain regions that are involved in antipsychotic efficacy.
Male and female rats were treated orally with aripiprazole (1mg/kg), olanzapine (1mg/kg), risperidone (0.3mg/kg) or vehicle 3 times/day starting from postnatal day 23 (±1day) for 20 days. Quantitative autoradiography was performed to examine the receptor binding densities.
Olanzapine significantly decreased 5-HT2A (5-HT2AR) and 5-HT2C receptor (5-HT2CR) binding in the prefrontal cortex (PFC), cingulate cortex (Cg) and nucleus accumbens (NAc) of both male and female rats. In the caudate putamen (CPu), olanzapine attenuated 5-HT2AR binding in both genders, and reduced 5-HT2CR binding in male rats. Olanzapine increased D2 receptor (D2R) binding in the NAcS of male rats, but decreased it in females. Olanzapine increased D1 receptor (D1R) binding in the Cg, while aripiprazole decreased D1R binding in the PFC of males. Aripiprazole significantly reduced 5-HT2AR binding in the male PFC. Risperidone decreased 5-HT2AR binding in the PFC of female rats, while attenuating D1R binding in the PFC and Cg of males. However, APDs have no effects on the binding of serotonin and dopamine transporters.
This study revealed that aripiprazole, olanzapine and risperidone affected 5-HT2AR, 5-HT2CR, 5-HTT, D1R and D2R bindings differently in the brains of juvenile male and female rats.
抗精神病药物（APDs）最初是用于治疗成人精神分裂症的；然而，它们越来越多地被用于儿童和青少年（大多为“非适应证用药”）。本研究旨在调查阿立哌唑、奥氮平和利培酮对参与抗精神病疗效的幼年大鼠脑区中5-羟色胺（5-HT）和多巴胺受体结合的影响。
从出生后第23天（±1天）开始，对雄性和雌性大鼠每天口服阿立哌唑（1mg/kg）、奥氮平（1mg/kg）、利培酮（0.3mg/kg）或赋形剂3次，持续20天。采用定量放射自显影法检测受体结合密度。
奥氮平显著降低了雄性和雌性大鼠前额叶皮质（PFC）、扣带回皮质（Cg）和伏隔核（NAc）中5-HT2A（5-HT2AR）和5-HT2C受体（5-HT2CR）结合。在尾状壳核（CPu）中，奥氮平减弱了两性的5-HT2AR结合，并降低了雄性大鼠的5-HT2CR结合。奥氮平增加了雄性大鼠NAcS中的D2受体（D2R）结合，但降低了雌性大鼠中的D2R结合。奥氮平增加了Cg中的D1受体（D1R）结合，而阿立哌唑降低了雄性大鼠PFC中的D1R结合。阿立哌唑显著降低了雄性PFC中的5-HT2AR结合。利培酮降低了雌性大鼠PFC中的5-HT2AR结合，同时减弱了雄性大鼠PFC和Cg中的D1R结合。然而，抗精神病药物对5-羟色胺和多巴胺转运体的结合没有影响。
本研究表明，阿立哌唑、奥氮平和利培酮对幼年雄性和雌性大鼠大脑中5-HT2AR、5-HT2CR、5-HTT、D1R和D2R结合的影响各不相同。
