Anxiolytic and Antidepressant-like Effects of Monoterpene Tetrahydrolinalool and In silico Approach of new Potential Targets

Introduction: Although drugs currently available for the treatment of anxiety and depression act through modulation of the neurotransmission systems involved in the neurobiology of the disorder, yet they often present side effects, which can impair patient adherence to treatment. Methods: This has driven the search for new molecules with anxiolytic and antidepressant potential. Aromatic plants are rich in essential oils, and their chemical constituents, such as monoterpenes, are being studied for these disorders. This study aims to evaluate the anxiolytic and antidepressant-like potential of the monoterpene tetrahydrolinalool in in vivo animal models and review pharmacological targets with validation through molecular docking. Male Swiss mice (Mus musculus) were treated with THL (37.5-600 mg kg^-1 p.o.) and submitted to the elevated plus maze, open field, rotarod, and forced swim tests. In the elevated plus-maze, THL at doses of 37.5 and 75 mg kg^-1 induced a significant increase in the percentage of entries (72.7 and 64.3% respectively), and lengths of stay (80.3 and 76.8% respectively) in the open arms tests. Results: These doses did not compromise locomotor activity or motor coordination in the animals. In the open field, rotarod tests, and the forced swimming model, treatment with THL significantly reduced immobility times at doses of 150, 300, and 600 mg kg^-1, and by respective percentages of 69.3, 60.9 and 68.7%. Conclusion: In molecular docking assay, which investigated potential targets, THL presented satisfactory energy values for: nNOs, SGC, IL-6, 5-HT1A, NMDAr, and D1. These demonstrate the potential of THL (a derivative of natural origin) in in vivo and in silico models, making it a drug candidate.