Melatonin Attenuates Morphine-induced Conditioned Place Preference in Wistar Rats

Overview

Journal Brain Behav

Specialty Psychology

Date 2021 Oct 28

PMID 34710287

Citations 3

Authors

Fahad S Alshehri

Badrah S Alghamdi

Alqassem Y Hakami

Abdullah A Alshehri

Yusuf S Althobaiti

Affiliations

Soon will be listed here.

Abstract

Purpose: Morphine is the predominantly used drug for postoperative and cancer pain management. However, the abuse potential of morphine is the primary disadvantage of using opioids in pain management. Melatonin is a neurohormone synthesized in the pineal gland and is involved in circadian rhythms in mammals, as well as other physiological functions. Melatonin provenly attenuates alcohol-seeking and relapse behaviors in rats. Therefore, we aimed to investigate the involvement of the melatonergic system in attenuating morphine dependence.

Materials And Methods: Male Wistar rats were divided into three groups: control, morphine, and morphine + melatonin. Animals were habituated for 3 days, and the initial preference was evaluated. Following the initial preference, the control group received the vehicle and was placed for a 45-min session in the assigned chamber every day, alternating between the two chambers, for 8 days. The morphine group received a morphine injection (5 mg/kg, IP) and was placed for a 45-min session in the white chamber, for a total of four sessions. The morphine + melatonin group received the morphine injection (5 mg/kg, IP) for a total of four sessions over an 8-day period. In the posttest session, the control and morphine groups received a vehicle injection 30 min before placement in the conditioned place preference (CPP). The morphine + melatonin group received a single injection of melatonin (50 mg/kg, IP) 30 min before the preference test.

Results: Statistical analysis revealed that repeated administration of morphine for four sessions produced a significant increase in the CPP score in the morphine group compared to the control group. However, a single melatonin injection administered 30 min before the posttest attenuated morphine-seeking behavior and reduced morphine-induced place preference.

Conclusion: These findings provide novel evidence for the role of the melatonergic system as a potential target in modulating morphine-seeking behavior.

Citing Articles

Exploring the potential use of melatonin as a modulator of tramadol-induced rewarding effects in rats.

Hakami A, Alghamdi B, Alshehri F Front Pharmacol. 2024; 15:1373746.

PMID: 38738177 PMC: 11082292. DOI: 10.3389/fphar.2024.1373746.

Pharmacological Methods of Pain Management: Narrative Review of Medication Used.

Alorfi N Int J Gen Med. 2023; 16:3247-3256.

PMID: 37546242 PMC: 10402723. DOI: 10.2147/IJGM.S419239.

Melatonin attenuates morphine-induced conditioned place preference in Wistar rats.

Alshehri F, Alghamdi B, Hakami A, Alshehri A, Althobaiti Y Brain Behav. 2021; 11(12):e2397.

PMID: 34710287 PMC: 8671767. DOI: 10.1002/brb3.2397.

References

Spanagel R, Almeida O, Shippenberg T . Long lasting changes in morphine-induced mesolimbic dopamine release after chronic morphine exposure. Synapse. 1993; 14(3):243-5. DOI: 10.1002/syn.890140307. View

Payabvash S, Beheshtian A, Salmasi A, Kiumehr S, Ghahremani M, Tavangar S . Chronic morphine treatment induces oxidant and apoptotic damage in the mice liver. Life Sci. 2006; 79(10):972-80. DOI: 10.1016/j.lfs.2006.05.008. View

Alvarez V, Arttamangkul S, Dang V, Salem A, Whistler J, Von Zastrow M . mu-Opioid receptors: Ligand-dependent activation of potassium conductance, desensitization, and internalization. J Neurosci. 2002; 22(13):5769-76. PMC: 6758217. DOI: 20026560. View

Mendelson W, Gillin J, Dawson S, Lewy A, Wyatt R . Effects of melatonin and propranolol on sleep of the rat. Brain Res. 1980; 201(1):240-4. DOI: 10.1016/0006-8993(80)90793-3. View

Mestek A, Hurley J, Bye L, Campbell A, Chen Y, Tian M . The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C. J Neurosci. 1995; 15(3 Pt 2):2396-406. PMC: 6578163. View

Ashby Jr C, Paul M, Gardner E, Heidbreder C, Hagan J . Acute administration of the selective D3 receptor antagonist SB-277011A blocks the acquisition and expression of the conditioned place preference response to heroin in male rats. Synapse. 2003; 48(3):154-6. DOI: 10.1002/syn.10188. View

Fisher S, Sugden D . Endogenous melatonin is not obligatory for the regulation of the rat sleep-wake cycle. Sleep. 2010; 33(6):833-40. PMC: 2881717. DOI: 10.1093/sleep/33.6.833. View

Sun Y, Chen G, Zhou K, Zhu Y . A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats. J Vis Exp. 2018; (141). DOI: 10.3791/58384. View

Masubuchi S, Honma S, Abe H, Ishizaki K, Namihira M, Ikeda M . Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats. Eur J Neurosci. 2000; 12(12):4206-14. View

10.

Hashimoto K, Ueda S, Ehara A, Sakakibara S, Yoshimoto K, Hirata K . Neuroprotective effects of melatonin on the nigrostriatal dopamine system in the zitter rat. Neurosci Lett. 2011; 506(1):79-83. DOI: 10.1016/j.neulet.2011.10.053. View

11.

Achat-Mendes C, Ali S, Itzhak Y . Differential effects of amphetamines-induced neurotoxicity on appetitive and aversive Pavlovian conditioning in mice. Neuropsychopharmacology. 2005; 30(6):1128-37. DOI: 10.1038/sj.npp.1300675. View

12.

Alshehri F, Alghamdi B, Hakami A, Alshehri A, Althobaiti Y . Melatonin attenuates morphine-induced conditioned place preference in Wistar rats. Brain Behav. 2021; 11(12):e2397. PMC: 8671767. DOI: 10.1002/brb3.2397. View

13.

Conroy D, Hairston I, Arnedt J, Hoffmann R, Armitage R, Brower K . Dim light melatonin onset in alcohol-dependent men and women compared with healthy controls. Chronobiol Int. 2012; 29(1):35-42. PMC: 4258345. DOI: 10.3109/07420528.2011.636852. View

14.

Uz T, Arslan A, Kurtuncu M, Imbesi M, Akhisaroglu M, Dwivedi Y . The regional and cellular expression profile of the melatonin receptor MT1 in the central dopaminergic system. Brain Res Mol Brain Res. 2005; 136(1-2):45-53. DOI: 10.1016/j.molbrainres.2005.01.002. View

15.

Shavali S, Ho B, Govitrapong P, Sawlom S, Ajjimaporn A, Klongpanichapak S . Melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by increasing the release of beta-endorphin an endogenous opioid. Brain Res Bull. 2005; 64(6):471-9. DOI: 10.1016/j.brainresbull.2004.09.008. View

16.

Takahashi T, Vengeliene V, Spanagel R . Melatonin reduces motivation for cocaine self-administration and prevents relapse-like behavior in rats. Psychopharmacology (Berl). 2017; 234(11):1741-1748. DOI: 10.1007/s00213-017-4576-y. View

17.

Dai W, Liu X, Bao Y, Yan B, Jiang N, Yu B . Selective blockade of spinal D2DR by levo-corydalmine attenuates morphine tolerance via suppressing PI3K/Akt-MAPK signaling in a MOR-dependent manner. Exp Mol Med. 2018; 50(11):1-12. PMC: 6235923. DOI: 10.1038/s12276-018-0175-1. View

18.

Ballantyne J . Opioids for the Treatment of Chronic Pain: Mistakes Made, Lessons Learned, and Future Directions. Anesth Analg. 2017; 125(5):1769-1778. DOI: 10.1213/ANE.0000000000002500. View

19.

Song L, Wu C, Zuo Y . Melatonin prevents morphine-induced hyperalgesia and tolerance in rats: role of protein kinase C and N-methyl-D-aspartate receptors. BMC Anesthesiol. 2015; 15:12. PMC: 4350305. DOI: 10.1186/1471-2253-15-12. View

20.

Zisapel N . Melatonin-dopamine interactions: from basic neurochemistry to a clinical setting. Cell Mol Neurobiol. 2002; 21(6):605-16. PMC: 11533843. DOI: 10.1023/a:1015187601628. View