Ameliorative effects of varenicline and bupropion on morphine-induced conditioned place preference in rats
Abstract
Background: Rewarding properties of morphine constitue the principal reasons for drug-craving behaviors which appear during morphine addiction. Varenicline and bupropion were reported to have some positive effects on addictive substances by different studies. In this study, the effects of varenicline and bupropion on morphine rewarding properties were investigated via conditioned place preference (CPP) in rats.
Methods: Conditioning was performed by intraperitoneal (i.p.) administration of morphine (10 mg/kg, i.p., 1, 3, 5, and 7 days) and saline (2,4, 6, and 8 days). To evaluate the development of dependence, subcutaneous administration of varenicline (0.5, 1 and 2 mg/kg, s.c.) or bupropion (5, 10 and 20 mg/kg, i.p.) was carried out 15 minutes before the administration of morphine. To evaluate the expression of dependence, varenicline or bupropion was administered 15 minutes before the test on 9th day. To investigate the extinction of the reward effect, drugs were tested daily on days 14, 18, and 22 and evaluated for reinstatement on 23rd day.
Results: Systemic morphine administration statistically significant produced CPP. Varenicline and bupropion did not reduce the development of morphine-induced CPP. In addition, varenicline and bupropion decreased expression, reinstatement and accelerated the extinction of morphine-induced CPP. Unlike varenicline, bupropion statistically significant produced CPP and altered locomotor activity.
Conclusions: These data suggest that varenicline and bupropion may be useful therapeutic pharmacological agents to reduce morphine dependence. The results of our research provide preliminary evidence to highlight the importance of the effects of varenicline and bupropion on morphine dependence. In the future, it would be appropriate to conduct mechanistic studies to explain the underlying mechanisms by using different methods on the subject.
Keywords
Morphine , Dependence , Varenicline , Bupropion , CPP.
References
- 1. Zarrabian S, Riahi E, Karimi S, Razavi Y, Haghparast A. The potential role of the orexin reward system in future treatments for opioid drug abuse. Brain Res 2020; 1731, 146028.
- 2. Azadfard M, Huecker MR, Leaming JM. Opioid Addiction. In StatPearls; Treasure Island (FL): StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC., 2020.
- 3. Lee YH, Brown DL, Chen HY. Current Impact and Application of Abuse-Deterrent Opioid Formulations in Clinical Practice. Pain Physician 2017; 20 (7), E1003-e1023.
- 4. 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.
- 5. Allahverdiyev O, Nurten A, Enginar N. Assessment of rewarding and reinforcing properties of biperiden in conditioned place preference in rats. Behav Brain Res 2011; 225 (2), 642-645.
- 6. Klein JW. Pharmacotherapy for Substance Use Disorders. Med Clin North Am 2016; 100 (4), 891-910.
- 7. Crunelle CL, Miller ML, Booij J, van den Brink W. The nicotinic acetylcholine receptor partial agonist varenicline and the treatment of drug dependence: a review. Eur Neuropsychopharmacol 2010; 20 (2), 69-79.
- 8. McCaul ME, Wand GS, Kuwabara H, Dannals RF, Wong D, Xu X. The Relationship of Varenicline Agonism of α4β2 Nicotinic Acetylcholine Receptors and Nicotine-Induced Dopamine Release in Nicotine-Dependent Humans. Nicotine Tob Res 2020; 22 (6), 892-899.
- 9. Rezayof A, Zatali H, Haeri-Rohani A, Zarrindast MR. Dorsal hippocampal muscarinic and nicotinic receptors are involved in mediating morphine reward. Behav Brain Res 2006; 166 (2), 281-290.
- 10. Zarrindast MR, Farzin D. Nicotine attenuates naloxone-induced jumping behaviour in morphine-dependent mice. Eur J Pharmacol 1996; 298 (1), 1-6.