Kanes S J, Hitzemann B A, Hitzemann R J
Department of Psychiatry, State University of New York at Stony Brook.
J Pharmacol Exp Ther. 1993 Oct;267(1):538-47.
The present study assesses the relationships among ED50 to neuroleptic-induced catalepsy and regional brain D1 and D2 dopamine receptor binding for eight inbred strains of mice (A, AKR, BALB/c, C3H, C57BL/6, CBA, DBA/2 and LP). The ED50 for haloperidol among these strains varies 30-fold from the most sensitive (BALB/c 0.31 mg/kg) to least sensitive (LP 9.5 mg/kg). As measured by quantitative receptor autoradiography, the haloperidol ED50 shows a significant positive correlation with [3H]spiroperidol binding to somatodendritic autoreceptors in the midbrain dopamine cell groups (A8, A9 and A10), but not with binding in the striatum. Although there are strain differences in [3H]SCH23390 binding in all regions studied, D1 receptor density was not correlated with haloperidol ED50. Within the striatum of these eight strains, there is no correlation between [3H]spiroperidol binding and [3H]SCH23390 binding. Overall, these data indicate that sensitivity to neuroleptic induced catalepsy is a genetically determined trait and that midbrain D2 receptor density may contribute significantly to the variance in this response.
本研究评估了八种近交系小鼠（A、AKR、BALB/c、C3H、C57BL/6、CBA、DBA/2和LP）中，致僵剂量50%（ED50）与抗精神病药物诱导的僵住症以及脑区D1和D2多巴胺受体结合之间的关系。这些品系中氟哌啶醇的ED50从最敏感的品系（BALB/c，0.31毫克/千克）到最不敏感的品系（LP，9.5毫克/千克）相差30倍。通过定量受体放射自显影法测量，氟哌啶醇的ED50与中脑多巴胺细胞群（A8、A9和A10）中[3H]螺哌啶醇与树突体自身受体的结合呈显著正相关，但与纹状体中的结合无关。尽管在所研究的所有区域中，[3H]SCH23390的结合存在品系差异，但D1受体密度与氟哌啶醇的ED50无关。在这八个品系的纹状体内，[3H]螺哌啶醇结合与[3H]SCH23390结合之间没有相关性。总体而言，这些数据表明，对抗精神病药物诱导的僵住症的敏感性是一种由基因决定的性状，并且中脑D2受体密度可能对这种反应的差异有显著贡献。
