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Targeting Orexin System as a Potential Treatment for Opioid Dependence
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Niloofar Aghajani   , Hossein Azizi , Saeed Semnaninan |
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Abstract: (229 Views) |
Introduction: Opioid addiction is a significant public health concern, and current treatments for this concern have limited efficacy and are associated with several side effects, highlighting the need for new therapeutic options to manage opioid dependence. As orexin is a neuropeptide that regulates various physiological processes, including sleep and arousal and it also play a role in opioid addiction and withdrawal, this study aimed to investigate the effect of blocking orexin type 1 receptors (OX1Rs) on naloxone-induced activation of neurons in the locus coeruleus (LC) of morphine-dependent rats.
Methods and Materials: Rats were made dependent on morphine (S.C. 10 mg/kg, BID, 12 h interval for ten consecutive days) and thereafter given either an orexin-1 receptor (OX1R) antagonist (SB-334867) or a control solution. After receiving naloxone, the activation of LC neurons was measured using single unit recording technique.
Results: The results obtained showed that OX1R antagonist treatment reduced the naloxone-induced activation of LC neurons in morphine-dependent rats. This finding suggests that OX1Rs may play a role in modulating the effects of naloxone in opioid-dependent individuals. Naloxone is an opioid antagonist used to reverse the effects of opioid overdose. However, it can also trigger withdrawal symptoms in opioid-dependent individuals, limiting its effectiveness.
Conclusion: The study's findings suggest that OX1R antagonists may be a potential therapeutic target for treating opioid dependence. By reducing the activation of LC neurons, OX1R antagonists could attenuate the severity of withdrawal symptoms and potentially prevent relapse, offering an alternative tool to currently available treatments for opioid addiction. However, caution must be taken with this approach, as the long-term safety and effectiveness of OX1R antagonists in human populations are not yet fully known. Additionally, further studies are needed to determine the optimal dosing and administration of OX1R antagonists and their potential interactions with other drugs used to treat opioid addiction
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| Keywords: Orexin, addiction, rats |
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Full-Text [PDF 259 kb]
(34 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/02/9 | Accepted: 2023/08/23 | Published: 2023/08/23
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