Department of Pharmacology, Institute of Psychiatry and Neurology, ul. Sobieskiego 9, 02-957, Warsaw, Poland.
Department of Psychiatry, Warsaw Medical University, Nowowiejska 27, 00-665, Warsaw, Poland.
Psychopharmacology (Berl). 2022 Dec;239(12):3847-3857. doi: 10.1007/s00213-022-06253-y. Epub 2022 Oct 24.
We have discovered that rats at the age of 18 months begin to twitch their heads spontaneously (spontaneous head twitching, SHT). To date, no one has described this phenomenon.
The purpose of this study was to characterize SHT pharmacologically and to assess some possible mechanisms underlying SHT.
Wistar male rats were used in the study. Animals at the age of 18 months were qualified as HSHT (SHT ≥ 7/10 min observations) or LSHT (SHT < 7/10 min observations). Quantitative real-time PCR with TaqMan low-density array (TLDA) approach was adopted to assess the mRNA expression of selected genes in rat's hippocampus.
HSHT rats did not differ from LSHT rats in terms of survival time, general health and behavior, water intake, and spontaneous locomotor activity. 2,5-dimethoxy-4-iodoamphetamine (DOI) at a dose of 2.5 mg/kg increased the SHT in HSHT and LSHT rats, while ketanserin dose-dependently abolished the SHT in the HSHT rats. The SHT was reduced or abolished by olanzapine, clozapine, risperidone, and pimavanserin. All these drugs have strong 5-HT2A receptor-inhibiting properties. Haloperidol and amisulpride, as antipsychotic drugs with a mostly dopaminergic mechanism of action, did not influence SHT. Similarly, escitalopram did not affect SHT. An in-depth gene expression analysis did not reveal significant differences between the HSHT and the LSHT rats.
SHT appears in some aging rats (about 50%) and is permanent over time and specific to individuals. The 5-HT2A receptor strongly controls SHT. HSHT animals can be a useful animal model for studying 5-HT2A receptor ligands.
我们发现，18 个月大的大鼠开始自发性地抽动头部（自发性头部抽动，SHT）。迄今为止，还没有人描述过这种现象。
本研究旨在对 SHT 进行药理学特征描述，并评估 SHT 潜在的一些机制。
研究使用 Wistar 雄性大鼠。18 个月龄的动物被分为 HSHT（SHT≥7/10 分钟观察）或 LSHT（SHT<7/10 分钟观察）。采用 TaqMan 低密度阵列（TLDA）定量实时 PCR 方法评估大鼠海马中选定基因的 mRNA 表达。
HSHT 大鼠在存活时间、一般健康和行为、饮水量和自发运动活动方面与 LSHT 大鼠无差异。2,5-二甲氧基-4-碘苯丙胺（DOI）2.5mg/kg 剂量增加了 HSHT 和 LSHT 大鼠的 SHT，而酮色林呈剂量依赖性地消除了 HSHT 大鼠的 SHT。奥氮平、氯氮平、利培酮和吡莫烷嗪降低或消除了 SHT。所有这些药物均具有强烈的 5-HT2A 受体抑制特性。作为主要作用于多巴胺能机制的抗精神病药物，氟哌啶醇和氨磺必利不影响 SHT。同样，艾司西酞普兰也不影响 SHT。深入的基因表达分析并未显示 HSHT 和 LSHT 大鼠之间存在显著差异。
SHT 出现在一些老年大鼠（约 50%）中，并且随着时间的推移是永久性的，且具有个体特异性。5-HT2A 受体强烈控制 SHT。HSHT 动物可作为研究 5-HT2A 受体配体的有用动物模型。
