Buprenorphine reduces somatic withdrawal in a mouse model of early-life morphine exposure.

Abstract

The rising prevalence of early-life opioid exposure has become a pressing public health issue in the U.S. Neonates exposed to opioids in utero are at risk of experiencing a constellation of postpartum withdrawal symptoms commonly referred to as neonatal opioid withdrawal syndrome (NOWS). Buprenorphine (BPN), a partial agonist at the mu-opioid receptor (MOR) and antagonist at the kappa-opioid receptor (KOR), is currently approved to treat opioid use disorder in adult populations. Recent research suggests that BPN may also be effective in reducing withdrawal symptoms in neonates who were exposed to opioids in utero. We sought to determine whether BPN attenuates somatic withdrawal in a mouse model of NOWS. Our findings indicate that the administration of morphine (10mg/kg, s.c.) from postnatal day (PND) 1-14 results in increased somatic symptoms upon naloxone-precipitated (1mg/kg, s.c.) withdrawal. Co-administration of BPN (0.3mg/kg, s.c.) from PND 12-14 attenuated symptoms in morphine-treated mice. On PND 15, 24h following naloxone-precipitated withdrawal, a subset of mice was examined for thermal sensitivity in the hot plate test. BPN treatment significantly increased response latency in morphine-exposed mice. Lastly, neonatal morphine exposure elevated mRNA expression of KOR, and reduced mRNA expression of corticotropin-releasing hormone (CRH) in the periaqueductal gray when measured on PND 14. Altogether, this data provides support for the therapeutic effects of acute low-dose buprenorphine treatment in a mouse model of neonatal opioid exposure and withdrawal.

• Authors: Gina Lepore, Theresa Morley-McLaughlin, Natalie Davidson, Caitlin Han, Cynthia Masese, Grace Reynolds, Victoria Saltz, Shivon A Robinson
• Journal: Drug and alcohol dependence (Drug Alcohol Depend) Vol. 248 Pg. 109938 (Jul 01 2023) ISSN: 1879-0046 [Electronic] Ireland
• PMID: 37267743 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Buprenorphine
• Morphine
• Analgesics, Opioid
• Naloxone
• Receptors, Opioid
• RNA, Messenger
• Narcotic Antagonists

Topics

• Female
• Mice
• Animals
• Buprenorphine (pharmacology, therapeutic use)
• Morphine (pharmacology)
• Analgesics, Opioid (pharmacology)
• Naloxone (pharmacology)
• Substance Withdrawal Syndrome (drug therapy, metabolism)
• Receptors, Opioid
• RNA, Messenger
• Narcotic Antagonists (pharmacology, therapeutic use)