Preclinical evaluation of thymol in alcohol withdrawal-induced behavioral and motor deficits in mice

Background: Alcohol withdrawal (AWD) induces central nervous system hyperexcitability, leading to anxiety, depression, and motor dysfunction, primarily via dysregulation of GABAergic, glutamatergic, and monoaminergic systems. Thymol, a monoterpenoid phenol from Thymus vulgaris, possesses documented GABAA receptor modulatory, anxiolytic, antioxidant, and anti-inflammatory properties. This study evaluated thymol's protective effects against AWD-induced neurobehavioral abnormalities in mice.
Material and Methods: Adult male Swiss albino mice were divided into six groups (n = 6/group): Control (CON) - vehicle-treated, Ethanol Withdrawal (EW) - 10% ethanol at 2 g/kg p.o. for 10 days, followed by abrupt withdrawal + Thymol 10 (EW-T10)- 10 mg/kg p.o. Thymol during withdrawal, EW+ Thymol 30 (EW-T30)-30 mg/kg p.o. thymol during withdrawal, Thymol 10 (T10) and Thymol 30 (T30) - Thymol only, no ethanol exposure. behavioural testing was performed 24 hours post-withdrawal using: Elevated Plus Maze (EPM), Open Field Test (OFT), and Light-Dark Test (LDT) for anxiety-like behaviour, Hole Board Test (HBT) for exploratory activity, Marble Burying Test (MBT) for compulsive/anxiety-linked behavior, Tail Suspension Test (TST) for depressive-like behavior, Stumbling and rotarod test for motor incoordination. Statistical analysis was conducted using one-way ANOVA followed by Tukey's post hoc test (p<0.05).
Results: AWD significantly increased anxiety-like behavior (EPM, OFT, LDT), compulsive behavior (MBT), depressive-like behavior (TST), and motor incoordination, while reducing exploration (HBT). Thymol treatment (10 and 30 mg/kg) significantly reversed these alterations in a dose-dependent manner. The higher dose (EW-T30) showed near-complete behavioral restoration. Thymol alone caused no adverse effects.
Conclusion: Conclusion: Thymol exhibits significant neuroprotective effects against alcohol withdrawal-induced anxiety, depression, and motor deficits in mice. Its likely mechanism involves positive modulation of GABA-A receptors, attenuation of oxidative stress, and restoration of neurotransmitter homeostasis. These findings support thymol's potential as a phytopharmacological agent for managing alcohol withdrawal syndrome and its neuropsychiatric sequelae.