چکیده
Background: Blighia sapida is a common plant consumed as vegetable in southern part of Nigeria. The ackee plant has a long history of use as a medicinal plant by several ethnic groups to treat a wide variety of Central Nervous System (CNS) disorders. The present study was designed to evaluate the antipsychotic effect of ethanol extract of Blighia sapida (Sapindaecea) stem bark in ameliorating psychotic features in mice.
Materials and methods: Graded doses of ethanol extract of Blighia sapida (EEBS) (10, 20, 40, 80 mg/kg, i.p) were administered 30 minutes prior to apormorphine (1 mg/kg, i.p) or ketamine (10 mg/kg, i.p). The animals were subsequently subjected to forced swim test to determine the effect of EEBS on ketamine enhanced immobility. Catalepsy and ptosis in the experimental mouse model were also assessed for probable side effects associated with antipsychotics. Doses of EEBS being tested and haloperidol (1 mg/kg) were administered intraperitoneally to animals (i.p) 30 minutes prior to the catalepsy and ptosis observation. Catalepsy was measured using the bar test, ptosis for each animal was evaluated in a transparent observation chamber at 30, 60, and 90 minutes post-treatment with EEBS or haloperidol.
Results: Ethanol extract of Blighia sapida stem bark (20, 40, 80 mg/kg, i.p) significantly decreased stereotyped behaviours induced by apomorphine (1mg/kg, i.p) and ketamine (10mg/kg, i.p) in a dosedependent manner, as 10 mg/kg EEBS failed to significantly inhibit ketamine induced stereotyped behaviours. EEBS showed differential effects against the ketamine induced hyperactivity compared to negative control. EEBS significantly (p< 0.05) reduced the ketamine enhanced immobility in the forced swim test and did not show extra-pyramidal side effects in the bar test of catalepsy. EEBS at higher doses induced ptosis that is commonly observed with most antipsychotics.
Conclusion: Ethanol extract of Blighia sapida stem bark reduced apomorphine and ketamne induced
stereotypy and hyperactivity in mice model suggesting its potential antipsychotic activity.
Keywords: Blighia sapida, Psychosis, Apormorphine, Ketamine, and Stereotypy
Abstrait
Contexte: Blighia sapida est une plante commune consommée comme légume dans la partie sud du
Nigéria. La plante ‘ackee’ est utilisée depuis longtemps comme plante médicinale par plusieurs groupes
ethniques pour traiter une grande variété de troubles du système nerveux central (SNC). La présente étude
a été conçue pour évaluer l’effet antipsychotique de l’extrait à l’éthanol de l’écorce de la tige
de Blighia sapida (Sapindaecea) dans l’amélioration des caractéristiques psychotiques chez les souris.
Matériaux et méthodes: Doses graduées d’extrait à l’éthanol de Blighia sapida (EEBS) (10, 20, 40, 80 mg / kg, ip) ont été administrés 30 minutes avant l’apomorphine (1 mg / kg, ip) ou la kétamine (10 mg / kg, ip). Les animaux ont ensuite été soumis à un test de nage forcée pour déterminer l’effet de l’EEBS sur l’immobilité accrue par la kétamine. La catalepsie et le ptosis dans le modèle expérimental chez la souris ont également été évalués pour déterminer les effets secondaires probables associés aux antipsychotiques. Des doses d’EEBS à l’essai et d’halopéridol (1 mg / kg) ont été administrées par voie intrapéritonéale aux animaux (ip) 30 minutes avant l’observation de la catalepsie et du ptosis. La catalepsie a été mesurée à l’aide du test de barre, le ptosis de chaque animal a été évalué dans une chambre d’observation transparente 30, 60 et 90 minutes après le traitement avec l’EEBS ou l’halopéridol.
Résultats: L’extrait d’éthanol de l’écorce de la tige de Blighia sapida (20, 40, 80 mg / kg, ip ) diminuait significativement les comportements stéréotypés induits par l’apomorphine (1 mg / kg, ip) et la kétamine (10 mg / kg, ip ) en fonction de la dose, comme 10 mg/kg d’EEBS n’a pas réussi à inhiber de manière significative les comportements stéréotypés induits par la kétamine . EEBS a montré des effets différentiels contre l’hyperactivité induite par la kétamine par rapport au control négatif. Les EEBS ont significativement (p <0,05) réduit l’immobilité accrue par la kétamine dans le test de nage forcée et n’ont pas montré d’effets secondaires extra-pyramidaux dans le test de barre de catalepsie. EEBS à des doses plus élevées a induit un ptosis qui est couramment observé avec la plupart des antipsychotiques.
Conclusion: L’extrait d’éthanol de l’écorce de la tige de Blighia sapida a réduit la stéréotypie et l’hyperactivité induite par l’apomorphine et la kétamine avec des modèles de souris suggérant son
activité antipsychotique potentiel.
Mots clés: Blighia sapida, psychose, apomorphine, kétamine et stéréotypie
Correspondence: Prof. F.A. Fehintola, Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria. E-mail: fentolamine@gmail.com
مراجع
Insel TR. Rethinking schizophrenia. Nature, 2010; 468:187-193.
Jablensky A. Epidemiology of schizophrenia: the global burden of disease and disability. Eur Arch Psychia Clin Neurosci, 2000; 250: 274-285.
McGorry PD, Singh BS, Connell S, et al. Diagnostic concordance in functional psychosis revisited: A study of inter-relationships between alternative concepts of psychotic disorder. Psychological Medicine, 1992; 22: 367-378.
Joel EH, Lee EL, Perry BM, Raymond WR and Alfred GG. Amphetamine In: Goodman and Gilman. The Pharmacological Basis of Therapeutics, 9th edition 1996; pp. 219-221.
Goff DC and Coyle JT. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. American Journal of Psychiatr, 2001; 158 (9): 1367–1375.
Jaspers K. General Psychopathology. Baltimore: The John Hopkins University Press 1997.
Beers MH and Robert B. Psychiatric Emergency. The Merck Manual of Diagnosis and Therapy. 2002; Section 15, Chap. 194, Merck Research Laboratories.Whitehouse Station, NJ.
Kapur S, Mizrahi R and Li M. From dopamine to salience to psychosis–linking biology, pharmacology and phenomenology of psychosis. Schizophr Res, 2005; 79: 59–68.
Creese I. Stimulants: neurochemical, behavioral, and clinical perspectives. New York: Raven Press 1983.
Segal DS, Geyer MA and Schuckit A. Stimulant-induced psychosis: an evaluation of animal models. In: Youdim MBH, Lovenberg W and Sharman DF, eds. Essays in neurochemistry and neuropharmacology. New York: John Wiley and Sons, 2000; 95–130.
Seeman P. Dopamine receptor and dopamine hypothesis of schizophrenia, Synapse, 1987; 1(2): 133-152.
Dworkin RH and Opler LA. Simple schizophrenia: Negative symptoms and refrontal hypodopaminergia. Ame J Psychiatry, 1992; 149: 1284-1285.
Javitt DC and Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry, 1991; 148: 1301–1308.
Krystal JH, Karper LP, Seibyl JP, et al. Subanestesic effects of the noncompetitive NMDA antagonist, Ketamine In humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Pyschiatry, 1994; 51: 199–214.
Malhotra AK, Pinals DA, Weingartner H, Sirocco K, Missar CD, Pickar D, et al. NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology, 1996; 14: 301–307.
Lahti AC, Holcomb HH, Medoff DR and Tamminga CA. Ketamine activates psychosis and alters limbic blood flow in schizophrenia. Neuroreport, 1995; 6: 869–872.
Malhotra AK, Pinals DA, Adler CM, et al. Ketamine induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsycho pharmacol, 1997; 17: 141–150.
Oleney JW and Farber NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry, 1995; 52(12): 998-1007.
Tandon R and Jibson MD. Extrapyramidal side effects of antipsychotic treatment: scope of problem and impact on outcome. Ann Clin Psychiatry, 2002; 14:123–129
Kapur S and Seeman P. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors: implications for atypical antipsychotic action. J. Psychiatry Neurosci; 2000; 25: 161–166.
Kapur S and Seeman P. Does fast dissociation from the dopamine d (2)receptor explain the action of atypical antipsychotics? a new hypothesis. Am J Psychiatry, 2001; 158: 360–369.
Coryell W, Miller DD and Perry PJ. Haloperidol plasma levels and dose optimization. Am J Psychiatry, 1998; 3(5): 241-253.
Volavka J, Cooper TB, Czobor P, et al. High dose treatment with haloperidol: the effect of dose reduction. J Clin Psychopharmacol, 2000; 20: 252–256
Okogun JI. The chemistry of Nigerian medicinal plants. Med Plant Res Nigeria, 1996; 10(5): 31–45.
Owonubi OM. Some pharmacological studies on Blighia Sapida. Med.Plant Res. Nigeria, 1996; 12: 187-195
Hamzah RU, Egwim EC, Kabiru AY and Muazu MB. Phytochemical and in vitro antioxidant properties of the methanolic extract of fruits of Blighia sapida, Vitellaria paradoxa and Vitex doniana. Oxidants and Antioxidants in Medical Science, 2013; 2(3), 217-223
Olusegun OJ and Olutomi OP. Chemical, Phytochemical and Antimicrobial Screening of Extracts of B. sapida for Agricultural and Medicinal Relevance. J. Nature and Sci, 2013; 11(10).
Susanta KR and Durga MK. A review on antiepileptic agents, current research and future prospectus on conventional and traditional drugs. Inter. Journal of Pharmaceutical sciences, 2010; 3:19-23.
Pandy V, Narasingam M and Mohamed Z. Antipsychotic-like activity of Noni (Morinda citrifolia Linn) in mice. BMC Complem Altern Med, 2012; 12: 186
Lorke DA. New approach to practical acute Toxicity Testing. Archie Toxicol, 1983; 54: 275 – 287
Bourin M, Poisson L and Larousse C. Piracetam interaction with neuroleptics in psycho-pharmacological tests. Neuropsychobiol, 1986; 19:93–96.
Kroczka B, Branski P, Palucha A, Pilc A and Nowak G. Antidepressant-like properties of zinc in rodent forced swim test. Brain Res Bull, 2001; 55: 297–300.
Jain NN, Ohal CC, Shroff SK, et al. Clitoria ternatea and the central nervous system. Pharmacol Biochem Behav, 2003; 75: 529–536
Costall B and Naylor R. Catalepsy and catatonia and the predictability of the cataleptic test for neuroleptics activity. Psychopharmacology (Berlin), 1974; 34: 233–241.
Bourin M, Poncelet M, Chermat R and Simon P. The value of the reserpine test in psychopharmacology. Arznei-Forschung, 1983; 33: 1173-1176.
Corbett R, Zhou L, Stephen M, Sorensen SM and Mondadori C. Animal models of negative symptoms; M100907 antagonizes PCP- induced immobility in a forced swim test in mice. Neuropsychopharmacology 1999; 21: 211-218
Costall B, Domeney AM and Naylor RJ. Behavioural and biochemical consequences of persistent overstimulation of mesolimbic dopamine systems in rat. Neuropharmacology, 1982; 21: 327–335
Roger DP, Paul CM and Vincent C. Behavioral Indices in Antipsychotic Drug Discovery. Journal Pharmacol Experimental Therapeutics, 2010; 333: 632– 638.
Johansson C, Jackson DM and Svensson L. The atypical antipsychotic, remoxipride, blocks phencyclidine-induced disruption of prepulse inhibition in the rat. Psychopharmacology, 1994; 116: 437–442.
Yamamoto M, Mizuki Y, Suetsugi M, et al. Effects of dopamine antagonistson changes in spontaneous EEG and locomotor activity in ketamine treated rats. Pharmacol Biochem Behav 1997; 57: 361-365.
Hoffmann DC. Typical and atypical neuroleptics antagonize MK-801- induced locomotion and stereotypy in rats. J Neural Transm Gen Sect, 1992; 89: 1–10.
Davis KL, Kahn RS, Ko G and Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry, 1991; 148: 1474-1486
Varty GB and Higgins GA. Examination of drug-induced and isolation induced disruptions of prepulse inhibition as models to screen antipsychotic drugs. Psychopharmacology, 1995; 122: 15–26.
Gimenez-liort L, Martinez E and Feree S. Different effects of dopamine antagonist on spontaneous and NMDA-induced motor activity in mice. Pharmacol Biochem Behav, 1997; 56: 549-553
Porsolt RD. Rodent models of depression: forced swimming and tail suspension behavioral despair tests in rats and mice. Curr Protoc Neurosci, 2001; 8(10A): 1-10.
Chatterjee M, Ganguly S, Srivastava M and Palit G. Effect of ‘chronic’ versus ‘acute’ ketamine administration and its ‘withdrawal’ effect on behavioural alterations in mice: implications for experimental psychosis. Behav Brain Res, 2011; 216: 247–254.
Page ME, Detke MJ, Kirby AD and Lucki I. Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology, 1999; 147: 62–67.
Weiner I, Schiller D, Gaisler-Salomon I, Green A and Joel D. A comparison of drug effects in latent inhibition and the forced swim test differentiates between the typical antipsychotic haloperidol, the atypical antipsychotics clozapine and olanzapine, and the antidepressants imipramine and paroxetine. Behav Pharmacol, 2003; 14: 215–222.
Crismon ML, Argo TR and Buckley PF. Schizophrenia In: Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG and Posey ML, editors. Pharmacotherapy: a pathophysiologic approach. 7th edition. McGraw-Hill Co. Inc., 2008; p. 1099–1122.
Becker A, Peters B, Schroeder H, et al. Ketamine-induced changes in rat behaviour: a possible animal model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry, 2003; 27: 687–700.
Gurevich EV and Joyce JN. Alterations in the cortical serotonergic system in schizophrenia: postmortem study. Biol.Psychiatry, 1997; 42: 529- 545.
Laruelle M, Abi-Dargham A, van Dyck C, et al. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [(123)I]beta-CIT. Biol Psychiatry, 2000; 47: 371–379.
Becker A, Peters B, Schroeder H, et al. Ketamine-induced changes in rat behaviour: a possible animal model of schizophrenia. Prog Neuro psychopharmacol Biol Psychiatry, 2003; 27: 687–700.
Kitaichi K, Yamada K, Hasegawa T, Furukawa H and Nabeshima T. Effects of risperidone on phencyclidine-induced behaviours: comparison with haloperidol and ritanserin; J Pharmacol, 1994; 66: 181–189.
Oka M, Noda Y, Ochi Y, et al. Pharmacological profile of AD 5423, a novel antipsychotic with both potent dopamine-D2 and serotonin-5HT2 antagonist properties. J Pharmacol Exp Ther 1993; 264: 158–165.
Chindo B, Adzu B, Yahaya T and Gamaniel K. Ketamine-enhanced immobility in forced swim test: A possible animal model for the negative symptoms of schizophrenia. Neuro-Psychopharmaco and Biol Psychia. 2012; 38: 310–316.
Porsolt RD, Moser PG and Castagne V. Behavioural indices in antipsychotic drug discovery. J Pharmacol Exp Therap, 2010; 333: 632-638.
Saidu AN, Mann A and Ndako M. Phytochemical studies and effect of the aqueous extract of Blighia sapida stem bark on the liver enzyme of albino rats. Inter Research J Biochem Bioinform 2013; 3(5): 104-108.