Investigation of the anxiolytic effect of rosmarinic acid

Anxiety disorders are among the most common psychiatric syndromes, with approximately one third of the population experiencing anxiety at some point in their lifetime. The search for effective and safe medications is ongoing. In this thesis, it was aimed to investigate the efficacy of rosmarinic acid, a natural phenolic compound, which has shown promise due to its pharmacological effects, on anxiety and whether the GABAergic system is involved in its possible effect. The effects of a single dose of 1, 2 and 4 mg/kg, i.p., rosmarinic acid and its administration for 14 days on anxiety behaviors in mice were evaluated by hole-board, light-dark and open-field tests, and the observed efficacy was compared with the efficacy of 1 mg/kg diazepam. To investigate the role of GABAergic system, 1 mg/kg, i.p., GABAA/BZ receptor antagonist flumazenil was pretreated. As a result of single dose administration and 14-day administration, it was observed that the most effective dose in terms of anxiolytic efficacy was 2 mg/kg and the observed effect was similar to diazepam. It was determined that most parameters evaluated with flumazenil pretreatment were antagonized and it was revealed that GABAergic modulation contributed to the efficacy. Moreover, the present anxiolytic activity applied at the single dose seems to be independent of locomotor activity. Preclinical data obtained from the thesis study indicate that rosmarinic acid is a promising active substance for the treatment of anxiety. However, preclinical studies need to be elaborated under different conditions in order to proceed to clinical studies.