A Comprehensive Approach to the Antidepressant-like Effect and Toxicity of Thunbergia alata Bojer ex Sims (Acanthaceae): Involvement of the Serotoninergic System

<b>Background</b>: <i>Thunbergia alata</i> is employed in traditional medicine to treat culture-bound syndromes such as "susto" (fright) or "espanto" (fearfulness). These conditions may correlate with depressive disorders. However, there is no evidence that this species has antidepressant properties. <b>Aims</b>: To characterize the antidepressant-like effect of an aqueous extract of <i>T. alata</i> in different paradigms and to analyze the role of brain monoamines in such actions. <b>Methods</b>: Independent groups of mice were treated with saline or the extract (1, 5, 10, 50, and 100 mg/kg; p.o.) and evaluated in the tail suspension (TST) and forced swimming tests (FST). Biochemical mechanisms were analyzed using inhibitors of monoamine synthesis, ligands of serotonergic receptors, and in vitro assays of MAO-A and MAO-B activity. Acute and sub-acute toxicity was evaluated. <b>Results</b>: The extract significantly reduced the immobility time of mice in both the TST and the FST, without affecting locomotor activity, as did the prototypical antidepressant desipramine. PCPA, AMPT, and NAN-190 abolished the extract's effects on despair, while serotonergic ligands (8-OH-DPAT, fluoxetine, and pindolol) facilitated their antidepressant action. <i>T. alata</i> inhibited MAO-A and B activity. High doses of the extract produced no change in organ morphology; LD₅₀ was >2000 mg/kg. <b>Conclusions</b>: This is the first study to demonstrate that an aqueous extract of <i>T. alata</i> produces antidepressant effects mediated by the monoamine brain levels, especially serotonin. In addition to its use in culture-bounded syndromes, the present findings of safety and efficacy give support to the proposal that <i>T. alata</i> may be used in the treatment of depression.