Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, Kraków, 31-343 Poland.
Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, Kraków, 31-343 Poland.
Neurosci Lett. 2019 Aug 10;707:134292. doi: 10.1016/j.neulet.2019.134292. Epub 2019 May 24.
The mechanisms underlying the beneficial effects of clozapine (CLZ) in the treatment of schizophrenia still remains far from clear. In the present work we studied the effect of CLZ on the dopamine D receptors (DR) in the mouse brain. CLZ was administered after ketamine (KET) in a paradigm strictly matching the one used in KET-induced attentional set-shifting task (ASST). It has been shown previously that CLZ reversed KET-induced cognitive impairments. In the present study we used in situ hybridization to estimate the level of mRNA, together with specific DR radioligand, [H]domperidone binding in the ventral tegmental area (VTA) as well as in the striatum, and observed an increase in the [H]domperidone binding in the striatum and an increase in DR mRNA level in the VTA following repeated (but not acute) CLZ administration in mice pre-treated repeatedly with KET. The obtained results allow for conclusion that CLZ in this experimental paradigm enhances biosynthesis of presynaptic DR.
氯氮平（CLZ）在治疗精神分裂症中的有益作用的机制仍远未明确。在本工作中，我们研究了 CLZ 对小鼠大脑中多巴胺 D 受体（DR）的影响。CLZ 在氯胺酮（KET）后给药，严格匹配用于 KET 诱导的注意定势转移任务（ASST）的范式。先前已经表明，CLZ 逆转了 KET 引起的认知障碍。在本研究中，我们使用原位杂交技术来估计 mRNA 水平，以及在腹侧被盖区（VTA）和纹状体中用[H]domperidone 结合特异性 DR 放射性配体，并观察到在重复（而非急性）CLZ 给药后，[H]domperidone 结合在纹状体中增加，并且在 VTA 中的 DR mRNA 水平增加，在重复用 KET 预处理的小鼠中。获得的结果表明，在这种实验范式中，CLZ 增强了突触前 DR 的生物合成。
