LAUSR

ABSTRACT Benzodiazepines are regularly prescribed for treatment of anxiety though there are side effects. Flavonoids have selective affinity for GABAA receptors implicated in anxiolytic‐like activity in rodents, but are devoid of the unwanted side effects of benzodiazepines. In this study, 6‐methoxyflavanone (6‐MeOF), a positive allosteric modulator of &ggr;‐amino butyric acid (GABA) responses at human recombinant GABAA receptors, was evaluated for its behavioral profile in the elevated plus‐maze as well as the staircase‐ plus and open‐field tests in mice. In addition, the distribution of 6‐MeOF in selected brain areas involved in anxiety (amygdala and cerebral cortex) was also examined using a validated high performance liquid chromatography ultraviolet detection (HPLC/UV) method. 6‐MeOF (10, 30 and 50 mg/kg) exerted an anxiolytic‐like effect, increasing entries and time spent in the open arm and the central platform, as well as head‐dipping frequency in the mouse elevated plus‐maze assay. It also decreased rearing incidence without suppressing the number of steps ascended in the staircase test. Whereas, in the open‐field anxiety test, 6‐MeOF had no effect on locomotor activity at lower doses, a decrease was observed at the highest dose (100 mg/kg). 6‐MeOF additionally produced an anxiolytic‐like increase in the time spent at the center of the open‐field apparatus. These effects were preferentially antagonized by pentylenetetrazole (15 mg/kg). Furthermore, pharmacokinetic studies disclosed a rapid appearance of 6‐MeOF in the plasma and discrete brain areas. Taken together, our findings suggest that 6‐MeOF readily crosses the blood brain barrier (BBB) generating anxiolytic activity, mediated through the GABAergic system.