Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction

The kappa opioid receptor (KOR) system has been linked to many types of drug addiction. An upregulation of the KOR leads to negative reinforcement effects which might contribute to drug relapse. Previously, our study has shown that a treatment combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg met...

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Main Authors: Wasli, Nur Syafinaz, Ridzwan, Irna Elina, Azzubaidi, Marwan Saad, Kasmuri, Abdul Razak, Ahmed, Qamar Uddin, Ming, Long Chiau, Mohamed, Nornisah
Format: Article
Language:English
Published: A and V Publication 2017
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Online Access:http://irep.iium.edu.my/63430/
http://irep.iium.edu.my/63430/
http://irep.iium.edu.my/63430/1/63430_Upregulation%20of%20kappa%20opioid%20receptor%20system.pdf
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spelling iium-634302018-04-16T04:19:40Z http://irep.iium.edu.my/63430/ Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction Wasli, Nur Syafinaz Ridzwan, Irna Elina Azzubaidi, Marwan Saad Kasmuri, Abdul Razak Ahmed, Qamar Uddin Ming, Long Chiau Mohamed, Nornisah RS Pharmacy and materia medica The kappa opioid receptor (KOR) system has been linked to many types of drug addiction. An upregulation of the KOR leads to negative reinforcement effects which might contribute to drug relapse. Previously, our study has shown that a treatment combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg methamphetamine (a partial nociceptin opioid peptide [NOP] agonist and mu/kappa antagonists) has successfully attenuated relapse in morphine/methamphetamine (poly-drug)-dependent mice using a conditioned place preference (CPP) model. Therefore, this recent research work aimed to further investigate the involvement of the KOR system in poly-drug relapse at the brain level. The CPP test procedure was repeated where the mice were conditioned with poly-drug (7.5 mg/kg morphine and 1.0 mg/kg methamphetamine). Following CPP test, the investigation was extended at the brain level by using an immunohistochemistry (IHC) technique. Rabbit monoclonal (EPR 18881) was used as it will bind specifically at the KOR. The level of the KOR is determined at two different stages of addiction; the post-conditioning (dependence) phase and reinstatement (relapse) phase. Four brain regions that have high expression of the KOR and involved in addiction circuits have been selected to be investigated. A significant increment of the KOR expression was seen in striatum during reinstatement compared to post-conditioning (33.39 ± 5.60 % and 16.73 ± 5.27 % respectively, p < 0.05, n = 12). While a significant reduction of the KOR expression during reinstatement compared to post-conditioning observed in the prefrontal cortex (35.07 ± 3.51 % and 44.09 ± 1.78 respectively, p < 0.01, n = 12), no significant changes were detected in hippocampus and amygdala. Surprisingly, the KOR was not affected in amygdala which regulates emotion. The KOR upregulation seen in the striatum suggests that this brain region might be triggered in order to oppose the stimulus-related reaction caused by this poly-drug. A and V Publication 2017-12-30 Article PeerReviewed application/pdf en http://irep.iium.edu.my/63430/1/63430_Upregulation%20of%20kappa%20opioid%20receptor%20system.pdf Wasli, Nur Syafinaz and Ridzwan, Irna Elina and Azzubaidi, Marwan Saad and Kasmuri, Abdul Razak and Ahmed, Qamar Uddin and Ming, Long Chiau and Mohamed, Nornisah (2017) Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction. Research Journal of Pharmacy and Technology, 10 (12). pp. 4488-4550. ISSN 0974-3618 E-ISSN 0974-360X http://rjptonline.org/AbstractView.aspx?PID=2017-10-12-79
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
topic RS Pharmacy and materia medica
spellingShingle RS Pharmacy and materia medica
Wasli, Nur Syafinaz
Ridzwan, Irna Elina
Azzubaidi, Marwan Saad
Kasmuri, Abdul Razak
Ahmed, Qamar Uddin
Ming, Long Chiau
Mohamed, Nornisah
Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction
description The kappa opioid receptor (KOR) system has been linked to many types of drug addiction. An upregulation of the KOR leads to negative reinforcement effects which might contribute to drug relapse. Previously, our study has shown that a treatment combination of 0.3 mg/kg buprenorphine and 1.0 mg/kg methamphetamine (a partial nociceptin opioid peptide [NOP] agonist and mu/kappa antagonists) has successfully attenuated relapse in morphine/methamphetamine (poly-drug)-dependent mice using a conditioned place preference (CPP) model. Therefore, this recent research work aimed to further investigate the involvement of the KOR system in poly-drug relapse at the brain level. The CPP test procedure was repeated where the mice were conditioned with poly-drug (7.5 mg/kg morphine and 1.0 mg/kg methamphetamine). Following CPP test, the investigation was extended at the brain level by using an immunohistochemistry (IHC) technique. Rabbit monoclonal (EPR 18881) was used as it will bind specifically at the KOR. The level of the KOR is determined at two different stages of addiction; the post-conditioning (dependence) phase and reinstatement (relapse) phase. Four brain regions that have high expression of the KOR and involved in addiction circuits have been selected to be investigated. A significant increment of the KOR expression was seen in striatum during reinstatement compared to post-conditioning (33.39 ± 5.60 % and 16.73 ± 5.27 % respectively, p < 0.05, n = 12). While a significant reduction of the KOR expression during reinstatement compared to post-conditioning observed in the prefrontal cortex (35.07 ± 3.51 % and 44.09 ± 1.78 respectively, p < 0.01, n = 12), no significant changes were detected in hippocampus and amygdala. Surprisingly, the KOR was not affected in amygdala which regulates emotion. The KOR upregulation seen in the striatum suggests that this brain region might be triggered in order to oppose the stimulus-related reaction caused by this poly-drug.
format Article
author Wasli, Nur Syafinaz
Ridzwan, Irna Elina
Azzubaidi, Marwan Saad
Kasmuri, Abdul Razak
Ahmed, Qamar Uddin
Ming, Long Chiau
Mohamed, Nornisah
author_facet Wasli, Nur Syafinaz
Ridzwan, Irna Elina
Azzubaidi, Marwan Saad
Kasmuri, Abdul Razak
Ahmed, Qamar Uddin
Ming, Long Chiau
Mohamed, Nornisah
author_sort Wasli, Nur Syafinaz
title Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction
title_short Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction
title_full Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction
title_fullStr Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction
title_full_unstemmed Upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction
title_sort upregulation of kappa opioid receptor system and its association with relapse to morphine/methamphetamine (poly-drug) addiction
publisher A and V Publication
publishDate 2017
url http://irep.iium.edu.my/63430/
http://irep.iium.edu.my/63430/
http://irep.iium.edu.my/63430/1/63430_Upregulation%20of%20kappa%20opioid%20receptor%20system.pdf
first_indexed 2023-09-18T21:29:57Z
last_indexed 2023-09-18T21:29:57Z
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