GABAA/benzodiazepine receptor complex mediates the anxiolytic-like effect of Montanoa tomentosa

Abstract

Ethnopharmacological relevance: Montanoa tomentosa also named Cihuapatli is a native plant of Mexico that has been used in traditional medicine for the last five centuries mainly as a remedy for reproductive impairments. However, there are reports indicating that this plant was also consumed by Mexican ancient people for its relaxing properties. In order to corroborate this information, the present study was conducted to evaluate the effect of Montanoa tomentosa lyophilisate (MT) on rat׳s anxiety-like behavior and to analyze its mechanism of action.

Materials and methods: The anxiolytic-like action of MT (1.5, 3.0, 6.0 and 12.0 mg/kg) was investigated in male Wistar rats tested in three animal models of anxiety: the burying behavior, the elevated plus maze and the hole-board tests. As a positive control, the anti-anxiety effects of different doses of the selective GABAA receptor agonist muscimol were also analyzed. In order to evaluate the participation of the GABAA and oxytocin receptors in the anxiolytic-like actions of MT, the GABAA receptors blockers picrotoxin (0.25 and 0.50 mg/kg), bicuculline (2.0 mg/kg) and flumazenil (5.00 and 10.0 mg/kg), the neurosteroid inhibitor finasteride (50.0 and 100 mg/kg) and the oxytocin receptor antagonist atosiban (0.25 µg) were used. Finally, to evaluate general activity, and motor coordination, the open field and rota-rod tests were used.

Results: MT at 3.0 mg/kg showed anxiolytic-like effects in the three anxiety paradigms without affecting reactivity, general motor activity or motor coordination; however, at higher doses sedative effects were observed. Picrotoxin (0.25 and 0.50 mg/kg), flumazenil (10.0 mg/kg) and finasteride (100 mg/kg) antagonized the anxiolytic-like actions of MT in the burying behavior test. In the plus maze and hole-board tests bicuculline (2.0 mg/kg) blocked the effects of the plant as well. Atosiban (0.25 µg) did not antagonize the anxiolytic-like actions of MT.

Conclusions: The results corroborate the anxiolytic-like actions of Montanoa tomentosa and suggest that this effect is mediated through GABAA receptors but not oxytocin receptors.

Keywords: Animal models of anxiety; Anxiolytic; Cihuapatli; GABA-A receptor; Oxytocin receptors.