Antidepressant-like properties of Antiaris toxicaria aqueous extract


  • Priscilla Kolibea Mante Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
  • Eric Woode Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
  • Kennedy K. E. Kukuia Department of Pharmacology, University of Ghana School of Pharmacy, College of Health Sciences, University of Ghana, Accra, Ghana
  • Donatus W. Adongo Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
  • Elvis O. Ameyaw Department of Biomedical and Forensic Sciences, School of Biological Science, University of Cape Coast, Cape Coast, Ghana


Antiaris, Para-chlorophenylalanine, Head twitches, N-methyl-d-aspartate, Tail suspension, Uterus


Background: Depression is a global burden whose therapy is plagued with inconsistent efficacy. Hence, the need for the discovery of newer therapies.

Methods: In this study, Antiaris toxicaria extract (200, 400 and 800 mg/kg, p.o.), was evaluated for antidepressant activity using behavioral tests battery particularly the forced swim test (FST) and tail suspension test (TST). In order to investigate its mechanism of action, animals groups were pretreated with α-methyldopa (α-MD), para-chlorophenylalanine (PCPA), reserpine, D-serine and 5-hydroxytryptophan.

Results: It increased the mobility periods and decreased immobility periods significantly in both the FST and the TST when compared to the control group. But the TST showed more promising effect than the FST. Pre-treatment with α-MD reversed the antidepressant property of A. toxicaria aqueous extract as did PCPA, reserpine and reserpine combined with α-MD. The extract increased the number of head twitches produced by 5-hydroxytryptophan confirming the involvement of serotonin in the antidepressant property and inhibited carbachol-induced contractions on the isolated rat uterus, which was non-competitively antagonized by propranolol.

Treatment with D-serine produced no significant increase in the immobility time produced by the extract at the doses studied. This excludes the involvement of N-methyl-d-aspartate in the possible mechanisms of action.

Conclusion: A. toxicaria possesses antidepressant-like action in rodents.


Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593-602.

Rybnikova E, Mironova V, Pivina S, Tulkova E, Ordyan N, Vataeva L, et al. Antidepressant-like effects of mild hypoxia preconditioning in the learned helplessness model in rats. Neurosci Lett. 2007;417(3):234-9.

Piato AL, Rizon LP, Martins BS, Nunes DS, Elisabetsky E. Antidepressant profile of Ptychopetalum olacoides Bentham (Marapuama) in mice. Phytother Res. 2009;23(4):519-24.

Abas M, Broadhead J. Mental disorders in the developing world. BMJ. 1994;308(6936):1052-3.

Nemeroff CB. The burden of severe depression: a review of diagnostic challenges and treatment alternatives. J Psychiatr Res. 2007;41(3-4):189-206.

Healy D. Did regulators fail over selective serotonin reuptake inhibitors? BMJ. 2006;333(7558):92-5.

Rates SM. Plants as source of drugs. Toxicon. 2001;39(5):603-13.

Mshana RN, Abbiw DK, Addae-Mensah I, Adjanouhoun E, Ahyi MRA, Ekpere JA, et al. Traditional Medicine and Pharmacopoeia; Contribution to the Revision of Ethnobotanical and Floristic Studies in Ghana. Accra, Ghana: Science and Technology Press, CSIR; 2001.

Levrier C, Kiremire B, Guéritte F, Litaudon M. Toxicarioside M. A new cytotoxic 10ß-hydroxy-19-nor-cardenolide from Antiaris toxicaria. Fitoterapia. 2012;83(4):660-4.

Li YN, Huang FY, Mei WL, Dai HF, Guo JL, Tan GH, et al. Toxicarioside A, isolated from tropical Antiaris toxicaria, blocks endoglin/TGF-ß signaling in a bone marrow stromal cell line. Asian Pac J Trop Med. 2012;5(2):91-7.

Mante PK, Adongo DW, Woode E, Kukuia KK, Ameyaw EO. Anticonvulsant effect of Antiaris toxicaria (Pers.) lesch. (Moraceae) aqueous extract in rodents. ISRN Pharmacol. 2013;2013:519208.

Agbaje EO, Ishola IO, Oniyire JA. Antidepressant, anxiolytic, and anticataleptic effects of aqueous leaf extract of Antiaris toxicaria Lesch. (Moraceae) in mice: possible mechanisms of actions. J Basic Clin Physiol Pharmacol. 2014.

Institute of Laboratory Animal Research, C.o.L.S., National Research Council. Guide for the Care and Use of Laboratory Animals. 7th edition. Washington, D.C: The National Academies Press; 1996.

Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977;266(5604):730-2.

Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 1985;85(5):367-70.

O’Leary OF, Bechtholt AJ, Crowley JJ, Hill TE, Page ME, Lucki I. Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology (Berl). 2007;192:357-71.

Poleszak E, Wlaź P, Szewczyk B, Wlaź A, Kasperek R, Wróbel A, et al. A complex interaction between glycine/NMDA receptors and serotonergic/noradrenergic antidepressants in the forced swim test in mice. J Neural Transm. 2011;118(11):1535-46.

Koe BK, Weissman A, Welch WM, Browne RG. Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine. a new uptake inhibitor with selectivity for serotonin. J Pharmacol Exp Ther. 1983;226(3):686-700.

Berrocoso E, Ikeda K, Sora I, Uhl GR, Sánchez-Blázquez P, Mico JA. Active behaviours produced by antidepressants and opioids in the mouse tail suspension test. Int J Neuropsychopharmacol. 2013;16(1):151-62.

Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, et al. Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology (Berl). 1997;132(2):107-24.

Millan MJ, Lejeune F, Gobert A. Reciprocal autoreceptor and heteroreceptor control of serotonergic, dopaminergic and noradrenergic transmission in the frontal cortex: relevance to the actions of antidepressant agents. J Psychopharmacol. 2000;14(2):114-38.

Brunello N, Mendlewicz J, Kasper S, Leonard B, Montgomery S, Nelson J, et al. The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. Eur Neuropsychopharmacol. 2002;12(5):461-75.

Stone EA, Lin Y, Rosengarten H, Kramer HK, Quartermain D. Emerging evidence for a central epinephrine-innervated alpha 1-adrenergic system that regulates behavioral activation and is impaired in depression. Neuropsychopharmacology. 2003;28(8):1387-99.

Gobert A, Rivet JM, Cistarelli L, Millan MJ. Potentiation of the fluoxetine-induced increase in dialysate levels of serotonin (5-HT) in the frontal cortex of freely moving rats by combined blockade of 5-HT1A and 5-HT1B receptors with WAY 100,635 and GR 127,935. J Neurochem. 1997;68(3):1159-63.

Oates JA, Gillespie L, Udenfriend S, Sjoerdsma A. Decarboxylase inhibition and blood pressure reduction by alpha-methyl-3,4-dihydroxy-DL-phenylalanine. Science. 1960;131(3417):1890-1.

Hess SM, Connamacher RH, Ozaki M, Udenfriend S. The effects of alpha-methyl-DOPA and alpha-methyl-metatyrosine on the metabolism of norepinephrine and serotonin in vivo. J Pharmacol Exp Ther. 1961;134:129-38.

Carlsson A, Lindqvist M. In-vivo decarboxylation of alpha-methyl DOPA and alpha-methyl metatyrosine. Acta Physiol Scand. 1962;54:87-94.

Sjoerdsma A. Alpha-methyldopa: antihypertensive drug with unusual mechanism of action. Heart Bull. 1963;12:1-4.

Hey JA, Ito T, Koss MC. alpha-Methyldopa produces mydriasis in the rat by stimulation of CNS alpha 2-adrenoceptors. Br J Pharmacol. 1988;94(3):834-8.

Metzger RR, Brown JM, Sandoval V, Rau KS, Elwan MA, Miller GW, et al. Inhibitory effect of reserpine on dopamine transporter function. Eur J Pharmacol. 2002;456(1-3):39-43.

Fukui M, Rodriguiz RM, Zhou J, Jiang SX, Phillips LE, Caron MG, et al. Vmat2 heterozygous mutant mice display a depressive-like phenotype. J Neurosci. 2007;27(39):10520-9.

Ortmann R, Martin S, Radeke E, Delini-Stula A. Interaction of beta-adrenoceptor agonists with the serotonergic system in rat brain. A behavioral study using the L-5-HTP syndrome. Naunyn Schmiedebergs Arch Pharmacol 1981;316(3):225-30.

Pandey DK, Rajkumar R, Mahesh R, Radha R. Depressant-like effects of parthenolide in a rodent behavioural antidepressant test battery. J Pharm Pharmacol. 2008;60(12):1643-50.

Elhwuegi AS. Central monoamines and their role in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(3):435-51.

Consoli D, Leggio GM, Mazzola C, Micale V, Drago F. Behavioral effects of the β3 adrenoceptor agonist SR58611A: is it the putative prototype of a new class of antidepressant/anxiolytic drugs? Eur J Pharmacol. 2007;573(1-3):139-47.

Mattsson H, Andersson T, Carlsson E, Hedberg A, Lundgren B, Olsson T. beta 1-and beta 2-adrenoceptor stimulatory effects of prenalterol. Naunyn Schmiedebergs Arch Pharmacol. 1982;321(4):302-8.

Tanaka Y, Horinouchi T, Koike K. New insights into beta-adrenoceptors in smooth muscle: distribution of receptor subtypes and molecular mechanisms triggering muscle relaxation. Clin Exp Pharmacol Physiol. 2005;32(7):503-14.

Liu YL, Nwosu UC, Rice PJ. Relaxation of isolated human myometrial muscle by beta2-adrenergic receptors but not beta1-adrenergic receptors. Am J Obstet Gynecol. 1998;179(4):895-8.

Levine J, Panchalingam K, Rapoport A, Gershon S, McClure RJ, Pettegrew JW. Increased cerebrospinal fluid glutamine levels in depressed patients. Biol Psychiatry. 2000;47(7):586-93.




How to Cite

Mante, P. K., Woode, E., Kukuia, K. K. E., Adongo, D. W., & Ameyaw, E. O. (2017). Antidepressant-like properties of Antiaris toxicaria aqueous extract. International Journal of Basic & Clinical Pharmacology, 4(1), 111–120. Retrieved from



Original Research Articles