Abstract
Tic disorder (TD) is a common neurodevelopmental disorder in children. Acute histamine deficiency may be involved in the pathogenesis of TDs. In this study, we demonstrate that histamine depletion exacerbates tic-like behaviors in a rat model of TD. Sprague–Dawley rats were divided into control, TD model, TD plus saline, and TD plus α-fluoromethylhistidine (α-FMH) groups. TD was induced by intraperitoneal iminodipropionitrile, and α-FMH was administered intracerebroventricularly. Behavioral assessments showed that α-FMH treatment significantly increased stereotyped and motor behavior scores compared with TD groups (p < 0.05). Immunohistochemistry revealed marked microglial activation in the striatum of TD groups, which was exacerbated by histamine deficiency. Striatal IL-6 and TNF-α levels were elevated in all TD groups; IL-6 was significantly higher in the α-FMH group than in TD groups (p < 0.05). Striatal dopamine receptor D2 (DRD2) expression was also upregulated in TD groups, with the highest levels observed after histamine depletion (p < 0.05). Liquid chromatography-tandem mass spectrometry result showed that glutamate levels were significantly reduced in the α-FMH group compared to the TD-NaCl group (p < 0.05). No significant differences were observed in the levels of dopamine, serotonin, or acetylcholine between the TD-NaCl and TD-α-FMH groups. Overall, our findings suggest that acute histamine deficiency aggravates TD-related behaviors by promoting neuroinflammation and upregulating DRD2 expression, highlighting the therapeutic potential of targeting histamine signaling in TD.
Get full access to this article
View all access options for this article.