THE ROLE OF MONOAMINERGIC SYSTEMS IN ANXIOLYTIC AND ANTI-DEPRESSANT POTENTIALS OF METHANOL EXTRACT OF ARTOCARPUS ALTILIS FOSBERG IN LABORATORY MICE

Abstract

Anxiety is described as a threat to psychological, physiological and behavioral state, while depression is a potentially life-threatening disorder that presents with decreased mood.Folkloric use of Artocarpus altilis includes alleviation of mood swings. Nevertheless, there is limited information on the scientific evaluation of the effects of the plant on anxiety and depression. Therefore, this study was designed to investigate the anxiolytic and antidepressant potentials of Artocarpus altilis in laboratory mice and the role of monoaminergic systems.

Artocarpus altilis was obtained from the Botanical Garden, University of Ibadan, authenticated at FRIN (FHI No.: 110483), shade-dried, pulverised and macerated in methanol for 72 hours to obtain Methanol Extract of Artocarpus altilis (MEAA). One hundred and eight male Swiss mice (18-25 g) were used in three studies (I, II and III). Study I had 5 groups (n=6) for anxiolytic and antidepressant studies. The anxiolytic effects of MEAA (50, 100 and 200 mg/kg, p.o.) were investigated using the Elevated Plus Maze (EPM), Elevated Zero Maze (EZM) and Light and Dark Test (LDT); while its antidepressant effects were evaluated using Forced Swimming Test (FST) and Tail Suspension Test (TST). Diazepam (1 mg/kg, i.p.) was used as the reference anxiolytic drug, imipramine (10 mg/kg p.o.) served as the reference antidepressant drug, while controls received normal saline. Study II had 4 groups (n=6); Imipramine, MEAA 50, 100 and 200 mg/kg, respectively, in which Lipopolysaccharide (0.5 mg/kg, i.p.) was used to induce depression. Reduced glutathione, Superoxide Dismutase (SOD), Nitric Oxide (NO) and Thiobarbituric Acid Reactive Substances (TBARS) were determined in brain tissue by standard methods using spectrophotometry. In study III, 4 groups (n=6) were used to test various mechanisms; Group 1 (200 mg/kg MEAA, 200-MEAA), Groups 2-4 were pre-treated with metergoline (5-HT receptor antagonist, 4 mg/kg, i.p.), prazosine (α1 adrenoceptor antagonist, 1 mg/kg, i.p.) and sulpiride (D2 receptor antagonist, 50 mg/kg, i.p), respectively before 200 mg/kg MEAA and TST. Data were subjected to descriptive statistics and analysed using ANOVA at α0.05.

The 200-MEAA showed significant increase in time spent in the open arms of EPM (63.0±11.0 s), EZM (74.5±10.2 s) and light chamber in LDT (123.3±1.2 s) relative to control (21.5±4.4; 53.7±0.3; 51.4±4.8 s). There was also a significant increase in the number of entries into the open arms of EPM (5.0±0.4), EZM (10.3±0.3) and LDT (5.0±0.4) relative to control (2.5±0.3; 5.3±0.9; 4.8±0.4). There was a significant decrease in immobility time in 200-MEAA in FST (28.8±4.9 s) and TST (61.3±7.5 s) relative to control (174±15.9; 174.2±6.9 s). Lipopolysaccharide+200-MEAA decreased immobility time in FST (38.2±11.1 s) relative to control (190.0±7.9 s). There were increases in the levels of TBARS (2.0±0.2 μmolMDA/g), SOD (24.6±0.9 ng/ml) and NO (144.9±7.3 μM/mg) in 200-MEAA relative to control (1.2±0.2 μmolMDA/g; 18.6±0.9 ng/ml and 128±5.8 μM/mg, respectively). In study III, there was a significant decrease in immobility time in 200-MEAA (170.3±7.7 s) when compared with metergoline, prazosine and sulpiride (200.5±18.5, 175.2±16.5, 184.3±11.3 s, respectively).

Methanol extract of Artocapus altilis demonstrated antidepressant and anxiolytic potentials. These effects are mediated through serotonergic, noradrenergic and dopaminergic receptors.