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The role of cannabinoid 1 receptor in the nucleus accumbens on tramadol induced conditioning and reinstatement.
Life Sci. 2020 Nov 01; 260:118430.LS

Abstract

AIMS

Previous investigations demonstrated that tramadol, as a painkiller, similar to morphine induces tolerance and dependence. Furthermore, the cannabinoid receptor 1 (CB1R) located in the nucleus accumbens (NAc) plays a critical role in morphine-induced conditioning. Therefore, the main objective of this study was to evaluate the role of NAc CB1R in tramadol induced conditioning and reinstatement.

MAIN METHODS

In the present experiment, the effect of NAc CB1 receptors on tramadol induced conditioning was tested by microinjecting of arachidonylcyclopropylamide (ACPA, CB1R agonist) and AM 251 (CB1R inverse agonist) in the NAc during tramadol-induced conditioning in the adult male Wistar rats. In addition, the role of NAc CB1R in the reinstatement was also evaluated by injecting ACPA and AM 251 after a 10-days extinction period.

KEY FINDINGS

The obtained data revealed that the administration of tramadol (1,2, and 4 mg/kg, ip) dose-dependently produced conditioned place preference (CPP). Moreover, intra-NAc administration of ACPA (0.25, 0.5, and 1 μg/rat) dose-dependently induced conditioning, while the administration of AM-251 (30, 60, and 120 ng/rat) induced a significant aversion. In addition, the administration of a non-effective dose of AM251 during tramadol conditioning inhibited conditioning induced by tramadol. On the other hand, the administration of ACPA after extinction induced a significant reinstatement. Notably, the locomotor activity did not change among groups.

SIGNIFICANCE

Previous studies have shown that tramadol-induced CPP occurs through μ-opioid receptors. The data obtained in the current study indicated that CB1R located in the NAc is involved in mediating conditioning induced by tramadol. Besides, CB1R also plays a vital role in the reinstatement of tramadol-conditioned animals. It might be due to the effect of opioids on enhancing the level of CB1R.

Authors+Show Affiliations

Pharmaceutical Sciences Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Institute, Tehran University of Medical Science, Tehran, Iran.. Electronic address: zarinmr@ams.ac.ir.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32931800

Citation

Sadeghi-Adl, Mahsa, et al. "The Role of Cannabinoid 1 Receptor in the Nucleus Accumbens On Tramadol Induced Conditioning and Reinstatement." Life Sciences, vol. 260, 2020, p. 118430.
Sadeghi-Adl M, Sadat-Shirazi MS, Shahini F, et al. The role of cannabinoid 1 receptor in the nucleus accumbens on tramadol induced conditioning and reinstatement. Life Sci. 2020;260:118430.
Sadeghi-Adl, M., Sadat-Shirazi, M. S., Shahini, F., Akbarabadi, A., Khalifeh, S., Borzabadi, S., Nasehi, M., & Zarrindast, M. R. (2020). The role of cannabinoid 1 receptor in the nucleus accumbens on tramadol induced conditioning and reinstatement. Life Sciences, 260, 118430. https://doi.org/10.1016/j.lfs.2020.118430
Sadeghi-Adl M, et al. The Role of Cannabinoid 1 Receptor in the Nucleus Accumbens On Tramadol Induced Conditioning and Reinstatement. Life Sci. 2020 Nov 1;260:118430. PubMed PMID: 32931800.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of cannabinoid 1 receptor in the nucleus accumbens on tramadol induced conditioning and reinstatement. AU - Sadeghi-Adl,Mahsa, AU - Sadat-Shirazi,Mitra-Sadat, AU - Shahini,Faezeh, AU - Akbarabadi,Ardeshir, AU - Khalifeh,Solmaz, AU - Borzabadi,Shokoofeh, AU - Nasehi,Mohammad, AU - Zarrindast,Mohammad-Reza, Y1 - 2020/09/13/ PY - 2020/02/25/received PY - 2020/08/27/revised PY - 2020/09/08/accepted PY - 2020/9/16/pubmed PY - 2020/11/28/medline PY - 2020/9/15/entrez KW - CB1 receptor KW - Conditioned place preference KW - Reinstatement KW - Tramadol SP - 118430 EP - 118430 JF - Life sciences JO - Life Sci VL - 260 N2 - AIMS: Previous investigations demonstrated that tramadol, as a painkiller, similar to morphine induces tolerance and dependence. Furthermore, the cannabinoid receptor 1 (CB1R) located in the nucleus accumbens (NAc) plays a critical role in morphine-induced conditioning. Therefore, the main objective of this study was to evaluate the role of NAc CB1R in tramadol induced conditioning and reinstatement. MAIN METHODS: In the present experiment, the effect of NAc CB1 receptors on tramadol induced conditioning was tested by microinjecting of arachidonylcyclopropylamide (ACPA, CB1R agonist) and AM 251 (CB1R inverse agonist) in the NAc during tramadol-induced conditioning in the adult male Wistar rats. In addition, the role of NAc CB1R in the reinstatement was also evaluated by injecting ACPA and AM 251 after a 10-days extinction period. KEY FINDINGS: The obtained data revealed that the administration of tramadol (1,2, and 4 mg/kg, ip) dose-dependently produced conditioned place preference (CPP). Moreover, intra-NAc administration of ACPA (0.25, 0.5, and 1 μg/rat) dose-dependently induced conditioning, while the administration of AM-251 (30, 60, and 120 ng/rat) induced a significant aversion. In addition, the administration of a non-effective dose of AM251 during tramadol conditioning inhibited conditioning induced by tramadol. On the other hand, the administration of ACPA after extinction induced a significant reinstatement. Notably, the locomotor activity did not change among groups. SIGNIFICANCE: Previous studies have shown that tramadol-induced CPP occurs through μ-opioid receptors. The data obtained in the current study indicated that CB1R located in the NAc is involved in mediating conditioning induced by tramadol. Besides, CB1R also plays a vital role in the reinstatement of tramadol-conditioned animals. It might be due to the effect of opioids on enhancing the level of CB1R. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/32931800/The_role_of_cannabinoid_1_receptor_in_the_nucleus_accumbens_on_tramadol_induced_conditioning_and_reinstatement_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(20)31183-8 DB - PRIME DP - Unbound Medicine ER -