Antkiewicz-Michaluk L, Karolewicz B, Michaluk J, Vetulani J
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Eur J Pharmacol. 1995 Dec 29;294(2-3):459-67. doi: 10.1016/0014-2999(95)00571-4.
We investigated the behavioral and biochemical events appearing in rats after withdrawal for 24 h or 8-12 days from two classical neuroleptics, haloperidol and pimozide. The neuroleptics were given for 14 days alone or shortly after injection of the Ca2+ channel blocker nifedipine. We have found that withdrawal effects after haloperidol and pimozide were different. After haloperidol treatment we observed an increase in cortical Ca2+ channel and limbic dopamine D1 receptor density and an increase in spontaneous motor activity and apomorphine-induced hyperactivity and stereotypy. In contrast no biochemical changes were observed during pimozide withdrawal, and locomotor activity and responses to apomorphine were depressed. Co-administration of nifedipine with haloperidol prevented the observed biochemical and behavioral symptoms of withdrawal. Nifedipine administration did not change the depressant effects of pimozide. Our results suggest that the voltage-dependent Ca2+ channel is involved in the observed withdrawal syndrome of neuroleptics, and that the absence of this syndrome after pimozide may be related to its considerable Ca2+ channel-blocking properties.
我们研究了大鼠在停用两种经典抗精神病药物氟哌啶醇和匹莫齐特24小时或8 - 12天后出现的行为和生化变化。单独给予抗精神病药物14天，或在注射钙通道阻滞剂硝苯地平后不久给予。我们发现氟哌啶醇和匹莫齐特停药后的效应不同。氟哌啶醇治疗后，我们观察到皮质钙通道和边缘多巴胺D1受体密度增加，自发运动活动、阿扑吗啡诱导的多动和刻板行为增加。相比之下，匹莫齐特停药期间未观察到生化变化，运动活动和对阿扑吗啡的反应受到抑制。硝苯地平与氟哌啶醇联合给药可预防观察到的停药生化和行为症状。硝苯地平给药并未改变匹莫齐特的抑制作用。我们的结果表明，电压依赖性钙通道参与了观察到的抗精神病药物停药综合征，匹莫齐特后该综合征的缺失可能与其显著的钙通道阻滞特性有关。
