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...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2021-05-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-88429-8 |
_version_ | 1818840685184286720 |
---|---|
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. |
first_indexed | 2024-12-19T04:14:07Z |
format | Article |
id | doaj.art-3398dfba11a247c8abe43f67d64910f4 |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-12-19T04:14:07Z |
publishDate | 2021-05-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Scientific Reports |
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 |
work_keys_str_mv | AT yusufsalthobaiti involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT farooqmalmutairi involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT fahadsalshehri involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT ebtehalaltowairqi involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT aliyahmmarghalani involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT amalaalghorabi involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT walaafalsanie involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT ahmedgaber involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT hashemoalsaab involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT atiahhalmalki involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT alqassemyhakami involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT turkialkhalifa involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT ahmaddalmalki involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT anamghardy involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin AT zahoorashah involvementofthedopaminergicsystemintherewardrelatedbehaviorofpregabalin |