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. 2020 Nov;12(Suppl 2):S826-S830.
doi: 10.4103/jpbs.JPBS_379_19. Epub 2020 Nov 5.

Striatum Hyperactivity Triggers Relapse to Morphine and Methamphetamine (Polydrug) Dependence in Mice

Nur Syafinaz Wasli  1 , Irna Elina Ridzwan  2   3 , Marwan Saad Azzubaidi  4 , Abdul Razak Kasmuri  1 , Qamar Uddin Ahmed  2 , Long Chiau Ming  5 , Nornisah Mohamed  6 , Syed Mohd Syahmi Syd Mohmad Faudzi  7
Affiliations

Striatum Hyperactivity Triggers Relapse to Morphine and Methamphetamine (Polydrug) Dependence in Mice

Nur Syafinaz Wasli et al. J Pharm Bioallied Sci. 2020 Nov.

Abstract

Introduction: κ-opioid receptor (KOPr) system has been linked to relapse to many substances, especially opioids. Positive responses were recently reported in morphine and methamphetamine (polydrug)-dependent mice treated with buprenorphine and naltrexone, a functional κ antagonist.

Objectives: This study aimed to determine the specific brain region that is responsive to KOPr treatment following polydrug dependence.

Materials and methods: The polydrug-dependent mice model was developed using conditioned place preference (CPP) method. Following successful withdrawal phase, the mice were treated with 0.3 mg/kg buprenorphine and 1.0 mg/kg naltrexone. Four brain regions (hippocampus, prefrontal cortex, amygdala, and striatum) were investigated using immunohistochemistry technique. This is to quantify the changes in KOPr expression in each major brain region that was primarily involved in addiction neurocircuits of many substances. Unpaired Student's t test was used to analyze all results, where P < 0.05 is considered significant.

Results: The results showed that treatment with buprenorphine and naltrexone successfully attenuated relapse in 60% of mice (n = 14). A significant upregulation of KOPr was detected in striatum at the end of post-withdrawal phase (P < 0.01, n = 12). This treatment successfully suppressed KOPr in striatum (P < 0.001, n = 12), which supports the positive results seen in the CPP setting. No significant changes were observed in other brain regions studied.

Conclusion: The hyperactivity of striatum suggests that the affected brain region following KOPr antagonist treatment is the region that primarily controls the drug rewarding activity, in which nucleus accumbens is located. This indicates that manipulation of KOPr system is one of the potential targets to treat morphine- or methamphetamine-dependence problem.

Keywords: Brain; drug addiction; kappa; methamphetamine; polydrug.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
The conditioned place preference test for morphine- and methamphetamine-dependent (polydrug) relapse model. *Significant difference from baseline (P < 0.05). Data were presented as mean ± SEM (n = 14) and analyzed using paired samples t test
Figure 2
Figure 2
The expression of κ opioid receptor in striatum during different stages of conditioned place preference. *Significant difference (P < 0.05) from post-conditioning. Data were presented as mean ± SEM and analyzed using unpaired samples t test
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