Exploring the Therapeutic Potential and Mechanism of Qiangzhi Fang in a Rat Model of Tic Disorder with ADHD: Behavioral and Molecular Insights

Background: Tic disorder (TD) frequently co-occurs with attention-deficit/hyperactivity disorder (ADHD) and is associated with greater symptom severity and limited treatment options. Qiangzhi Fang is a Traditional Chinese Medicine (TCM) herbal formula that has been clinically used for neurobehavioral disorders, but its experimental evidence and mechanisms remain insufficiently characterized. Objective: To evaluate the behavioral effects of Qiangzhi Fang in a drug-induced rat model of TD comorbid with ADHD and to explore potential striatal molecular mechanisms. Methods: A drug-induced TD+ADHD rat model was established in male Sprague-Dawley rats. Animals were assigned to control, model, and Qiangzhi Fang treatment groups (low, medium, and high doses). Behavioral assessments included stereotypic behavior scoring (tic-like behaviors), locomotor activity (hyperactivity), anxiety-related behavior, and spatial learning and memory. Striatal expression of tyrosine hydroxylase (TH) and phosphorylated Ca 2 ⁺/calmodulin-dependent protein kinase II (p-CaMKII) was examined using Western blotting and real-time PCR. Results: Qiangzhi Fang treatment ameliorated TD- and ADHD-like behavioral abnormalities, including reduced stereotypic movements, decreased hyperactivity, and improved spatial learning and memory performance, with the most pronounced effects observed at higher doses. At the molecular level, treatment was associated with downregulation of striatal TH and p-CaMKII expression. These markers reflect alterations in dopamine synthesis and synaptic signaling; however, dopamine levels, receptor subtypes, and neural circuitry were not directly assessed. Conclusion: Qiangzhi Fang improved behavioral phenotypes in a preclinical rat model of TD comorbid ADHD and was associated with changes in striatal TH and p-CaMKII expression. These findings suggest a possible neuromodulatory role of Qiangzhi Fang, although the mechanistic evidence remains preliminary. This study may provide an experimental basis for further investigation of herbal formulations in TD and ADHD.