Morinda citrifolia Linn. (Noni) fruit extract attenuates ethanol seeking behavior in mouse runway paradigm

Year 2020, Volume: 24 Issue: 5, 632 - 639, 27.06.2025

Yasmin Khan Vijayapandi Pandy

https://doi.org/10.35333/jrp.2020.218

Abstract

In this study, we used methanolic extract of Morinda citrifolia Linn. fruit (MMC) in order to find its effect against ethanol seeking behavior in a modified mouse runway paradigm. During conditioning/acquisition animals were treated with accelerated doses of ethanol (0.5-4 g/kg, i.p.) for 5 days (Day 1- Day 5). Then, ethanol seeking behavior was assessed on Day 6 (postconditioning test). Ethanol seeking behavior was confirmed in ethanol control group in which the run time to reach the target box was significantly decreased. The test drug MMC (1, 3, and 5 g/kg, p.o.) caused a significant reversal of the ethanol seeking behavior by increasing the run time to reach the goal box as seen with the reference drug acamprosate (ACAM; 300 mg/kg, p.o.) in mice. After postconditioning test, nonrewarded abolishment assays were performed for a period of five days (Day 7 –Day 11). After 5 days of abolishment (abstinence), a priming dose of ethanol (the highest dose at 1/5th portion applied in control (i.e. 0.8 g/kg, i.p.)) in house cage significantly reinstated the ethanol-seeking behavior. Interestingly, MMC at a higher dose (5 g/kg, p.o.) showed significant halt on ethanol-induced reinstatement in mice as shown with the reference drug ACAM (300 mg/kg, p.o.). The outcome of this study reveals that MMC alleviated ethanol seeking behaviour in modified mouse runway paradigm and it could be effectively used to treat alcohol dependence.

Keywords

Alcohol dependence , acamprosate , Morinda citrifolia Linn , mouse runway paradigm , selfadministration

References

• [1] Ettenberg A. The runway model of drug self-administration. Pharmacol Biochem Behav. 2009; 91: 271–277. [CrossRef]
• [2] Geist TD, Ettenberg A. A simple method for studying intravenous drug reinforcement in a runway. Pharmacol Biochem Behav. 1990; 36: 703–706. [CrossRef]
• [3] Pandy V, Khan Y. Design and development of a modified runway model of mouse drug self-administration. Sci Rep. 2016; 6, 21944. [CrossRef]
• [4] Dixon AR, McMillen H, Etkin NL. Ferment this: the transformation of Noni, a traditional Polynesian medicine (Morinda citrifolia, Rubiaceae). Econ Bot. 1999; 53(1): 51–68. [CrossRef]
• [5] Narasingam M, Vijeepallam K, Mohamed Z, Pandy V. Anxiolytic- and antidepressant-like activities of a methanolic extract of Morinda citrifolia Linn. (noni) fruit in mice: Involvement of benzodiazepine-GABAAergic, serotonergic and adrenergic systems. Biomed Pharmacother. 2017; 96: 944-952. [CrossRef]
• [6] Pandy V, Narasingam M, Mohamed Z. Antipsychotic-like activity of Noni (Morinda citrifolia Linn.) in mice. BMC Complement Altern Med. 2012; 12(1): 186. [CrossRef]
• [7] Narasingam M, Pandy V, Mohamed Z. Noni (Morinda citrifolia L.) fruit extract attenuates the rewarding effect of heroin in conditioned place preference but not withdrawal in rodents. Exp Anim. 2016; 65(2): 157–164. [CrossRef]
• [8] Khan Y, Pandy V. Methanolic Extract of Morinda citrifolia L. (Noni) Unripe Fruit Attenuates Ethanol-Induced Conditioned Place Preferences in Mice. Front Pharmacol. 2016; 7: 352. [CrossRef]
• [9] Pandy V, Wai YC, Roslan NFA, Sajat A, Jallb AHA, Vijeepallam K. Methanolic extract of Morinda citrifolia Linn. unripe fruit attenuates methamphetamine-induced conditioned place preferences in mice. Biomed Pharmacother. 2018; 107: 368-373. [CrossRef]
• [10] Pandy V, Khan Y. Noni (Morinda citrifolia Linn.) fruit juice attenuates the rewarding effect of ethanol in conditioned place preference in mice. Exp Anim. 2016; 65(4): 437–445. [CrossRef]
• [11] Issell BF, Franke A, Fielding RM. Pharmacokinetic study of Noni fruit extract. J Diet Suppl. 2008; 5: 373–382. [CrossRef]
• [12] Wang MY, West BJ, Jensen CJ, Nowicki D, Su C, Palu AK, Anderson G. Morinda citrifolia (Noni): a literature review and recent advances in Noni research. Acta Pharmacol. Sin. 2002; 23: 1127–1141.
• [13] Yang YF, Wei Xu, Song W, Ye M, Yang XW. Transport of Twelve Coumarins From Angelicae Pubescentis Radix Across a MDCK-pHaMDR Cell Monolayer-An in Vitro Model for Blood-Brain Barrier Permeability. Molecules. 2015; 25: 20(7): 11719-32. [CrossRef]
• [14] Zulissetiana KF, Susilawati. The Efficacy of Noni Fruit Methanol Extract (Morinda citrofolia) to Brain Derived Neurotrophic Factor (BDNF) on Male Swiss Webster Mice Induced By Immobilization Stress. Journal of Physics: Conf. Series 1095. 2018; 012013.
• [15] Muralidharan P, Srikanth J. Anti epileptic activity of Morinda citrifolia Linn fruit extract. J Chem. 2010; 7: 612–616. [CrossRef]
• [16] Schulte T, Oberlin BG, Kareken DA, Marinkovic K, Müller‐ Oehring EM, eyerhoff DJ, Tapert S. How acute and chronic alcohol consumption affects brain networks: insights from multimodal neuroimaging. Alcohol Clin Exp Res. 2012; 36(12): 2017–2027. [CrossRef]
• [17] Luo SX, Huang EJ. Dopaminergic neurons and brain reward pathways: from neurogenesis to circuit assembly. Am J Clin Pathol. 2016; 186(3): 478–488. [CrossRef]
• [18] Aguilar MA, Manzanedo C, Do Couto BR, Rodríguez-Arias M, Miñarro J. Memantine blocks sensitization to the rewarding effects of morphine. Brain Res. 2009; 1288: 95–104. [CrossRef]
• [19] Davis M, Myers KM. The role of glutamate and gamma-aminobutyric acid in fear extinction: clinical implications for exposure therapy. Biol Psychiatry. 2002; 52(10): 998–1007. [CrossRef]
• [20] Pandy V, Narasingam M, Kunasegaran T, Murugan DD, Mohamed Z. Effect of noni (Morinda citrifolia Linn.) fruit and its bioactive principles scopoletin and rutin on rat vas deferens contractility: an ex vivo study. ScientificWorldJournal. 2014; 2014: 909586. [CrossRef]
• [21] Pandy V, Narasingam M, Vijeepallam K, Mohan S, Mani V, Mohamed Z. The Ethyl Acetate Fraction of a Methanolic Extract of Unripe Noni (Morinda Citrifolia Linn.) Fruit Exhibits a Biphasic Effect on the Dopaminergic System in Mice. Exp Anim.2017; 5: 66(3): 283-291. [CrossRef]
• [22] Pandy V, Vijeepallam K. Antipsychotic-like activity of scopoletin and rutin against the positive symptoms of schizophrenia in mouse models. Exp Anim. 2017; 66 (4): 417-423. [CrossRef]
• [23] Bevins RA, Besheer J, Pickett KS. Nicotine-conditioned locomotor activity in rats: dopaminergic and gabaergic influences on conditioned expression. Pharmacol Biochem Behav. 2001; 68: 135-145. [CrossRef]
• [24] Kuzmin A, Sandin J, Terenius L, Ogren SO. Acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in mice: effects of opioid receptor-like 1 receptor agonists and naloxone. J Pharmacol Exp Ther. 2003; 304(1): 310–318. [CrossRef]
• [25] Mattioli L, Titomanlio F, Perfumi M. Effects of a Rhodiola rosea L. extract on the acquisition, expression, extinction, and reinstatement of morphine- induced conditioned place preference in mice. Psychopharmacology (Berl). 2012; 221(2): 183-193. [CrossRef]
• [26] Mueller D, Stewart J. Cocaine-induced conditioned place preference: reinstatement by priming injections of cocaine after extinction. Behav Brain Res. 2000; 115(1): 39–47. [CrossRef]
• [27] Spanagel R, Hölter SM, Allingham K, Landgraf R, Zieglgänsberger W. Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat. Eur J Pharmacol. 1996; 305 (1–3): 39–44. [CrossRef]a