Involvement of the dopaminergic system in the reward-related behavior of pregabalin

Abstract There has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned...

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Main Authors: Yusuf S. Althobaiti, Farooq M. Almutairi, Fahad S. Alshehri, Ebtehal Altowairqi, Aliyah M. Marghalani, Amal A. Alghorabi, Walaa F. Alsanie, Ahmed Gaber, Hashem O. Alsaab, Atiah H. Almalki, Alqassem Y. Hakami, Turki Alkhalifa, Ahmad D. Almalki, Ana M. G. Hardy, Zahoor A. Shah
Format: Article
Language:English
Published: Nature Portfolio 2021-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-88429-8
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author Yusuf S. Althobaiti
Farooq M. Almutairi
Fahad S. Alshehri
Ebtehal Altowairqi
Aliyah M. Marghalani
Amal A. Alghorabi
Walaa F. Alsanie
Ahmed Gaber
Hashem O. Alsaab
Atiah H. Almalki
Alqassem Y. Hakami
Turki Alkhalifa
Ahmad D. Almalki
Ana M. G. Hardy
Zahoor A. Shah
author_facet Yusuf S. Althobaiti
Farooq M. Almutairi
Fahad S. Alshehri
Ebtehal Altowairqi
Aliyah M. Marghalani
Amal A. Alghorabi
Walaa F. Alsanie
Ahmed Gaber
Hashem O. Alsaab
Atiah H. Almalki
Alqassem Y. Hakami
Turki Alkhalifa
Ahmad D. Almalki
Ana M. G. Hardy
Zahoor A. Shah
author_sort Yusuf S. Althobaiti
collection DOAJ
description Abstract There has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned place preference (CPP) paradigm. We observed that a 60 mg/kg dose could induce CPP in mice and that pregabalin-rewarding properties were mediated through glutamate neurotransmission. Notably, the dopaminergic reward circuitry is also known to play a crucial role in medication-seeking behavior. Therefore, this study aimed to explore the possible involvement of dopaminergic receptor-1 in pregabalin-induced CPP. Mice were randomly allocated to receive saline or the dopamine-1 receptor antagonist SKF-83566 (0.03 mg/kg, intraperitoneal). After 30 min, the mice received either saline or pregabalin (60 mg/kg) during the conditioning phase. Among the control groups that received saline or SKF-83566, the time spent in the two conditioning chambers was not significantly altered. However, among the pregabalin-treated group, there was a marked increase in the time spent in the drug-paired chamber compared to the time spent in the vehicle-paired chamber. Notably, blocking dopamine-1 receptors with SKF-83566 completely prevented pregabalin-induced place preference, thus demonstrating the engagement of the dopaminergic system in pregabalin-induced reward-related behavior.
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spelling doaj.art-3398dfba11a247c8abe43f67d64910f42022-12-21T20:36:21ZengNature PortfolioScientific Reports2045-23222021-05-011111910.1038/s41598-021-88429-8Involvement of the dopaminergic system in the reward-related behavior of pregabalinYusuf S. Althobaiti0Farooq M. Almutairi1Fahad S. Alshehri2Ebtehal Altowairqi3Aliyah M. Marghalani4Amal A. Alghorabi5Walaa F. Alsanie6Ahmed Gaber7Hashem O. Alsaab8Atiah H. Almalki9Alqassem Y. Hakami10Turki Alkhalifa11Ahmad D. Almalki12Ana M. G. Hardy13Zahoor A. Shah14Department of Pharmacology and Toxicology, College of Pharmacy, Taif UniversityAddiction and Neuroscience Research Unit, Taif UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, Taif UniversityAddiction and Neuroscience Research Unit, Taif UniversityAddiction and Neuroscience Research Unit, Taif UniversityAddiction and Neuroscience Research Unit, Taif UniversityAddiction and Neuroscience Research Unit, Taif UniversityAddiction and Neuroscience Research Unit, Taif UniversityAddiction and Neuroscience Research Unit, Taif UniversityCollege of Medicine, King Saud Bin Abdulaziz University for Health SciencesGeneral Administration for Precursors and Laboratories, General Directorate of Narcotics Control, Ministry of InteriorGeneral Administration for Precursors and Laboratories, General Directorate of Narcotics Control, Ministry of InteriorDepartment of Physiology and Pharmacology, College of Medicine and Life Sciences, University of ToledoDepartment of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of ToledoAbstract There has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned place preference (CPP) paradigm. We observed that a 60 mg/kg dose could induce CPP in mice and that pregabalin-rewarding properties were mediated through glutamate neurotransmission. Notably, the dopaminergic reward circuitry is also known to play a crucial role in medication-seeking behavior. Therefore, this study aimed to explore the possible involvement of dopaminergic receptor-1 in pregabalin-induced CPP. Mice were randomly allocated to receive saline or the dopamine-1 receptor antagonist SKF-83566 (0.03 mg/kg, intraperitoneal). After 30 min, the mice received either saline or pregabalin (60 mg/kg) during the conditioning phase. Among the control groups that received saline or SKF-83566, the time spent in the two conditioning chambers was not significantly altered. However, among the pregabalin-treated group, there was a marked increase in the time spent in the drug-paired chamber compared to the time spent in the vehicle-paired chamber. Notably, blocking dopamine-1 receptors with SKF-83566 completely prevented pregabalin-induced place preference, thus demonstrating the engagement of the dopaminergic system in pregabalin-induced reward-related behavior.https://doi.org/10.1038/s41598-021-88429-8
spellingShingle Yusuf S. Althobaiti
Farooq M. Almutairi
Fahad S. Alshehri
Ebtehal Altowairqi
Aliyah M. Marghalani
Amal A. Alghorabi
Walaa F. Alsanie
Ahmed Gaber
Hashem O. Alsaab
Atiah H. Almalki
Alqassem Y. Hakami
Turki Alkhalifa
Ahmad D. Almalki
Ana M. G. Hardy
Zahoor A. Shah
Involvement of the dopaminergic system in the reward-related behavior of pregabalin
Scientific Reports
title Involvement of the dopaminergic system in the reward-related behavior of pregabalin
title_full Involvement of the dopaminergic system in the reward-related behavior of pregabalin
title_fullStr Involvement of the dopaminergic system in the reward-related behavior of pregabalin
title_full_unstemmed Involvement of the dopaminergic system in the reward-related behavior of pregabalin
title_short Involvement of the dopaminergic system in the reward-related behavior of pregabalin
title_sort involvement of the dopaminergic system in the reward related behavior of pregabalin
url https://doi.org/10.1038/s41598-021-88429-8
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