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1.
Drug Alcohol Depend ; 248: 109938, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37267743

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.


Subject(s)
Buprenorphine , Substance Withdrawal Syndrome , Female , Mice , Animals , Buprenorphine/pharmacology , Buprenorphine/therapeutic use , Morphine/pharmacology , Analgesics, Opioid/pharmacology , Naloxone/pharmacology , Substance Withdrawal Syndrome/drug therapy , Substance Withdrawal Syndrome/metabolism , Receptors, Opioid , RNA, Messenger , Narcotic Antagonists/pharmacology , Narcotic Antagonists/therapeutic use
2.
Cell ; 186(3): 577-590.e16, 2023 02 02.
Article in English | MEDLINE | ID: mdl-36693373

ABSTRACT

Pleasurable touch is paramount during social behavior, including sexual encounters. However, the identity and precise role of sensory neurons that transduce sexual touch remain unknown. A population of sensory neurons labeled by developmental expression of the G protein-coupled receptor Mrgprb4 detects mechanical stimulation in mice. Here, we study the social relevance of Mrgprb4-lineage neurons and reveal that these neurons are required for sexual receptivity and sufficient to induce dopamine release in the brain. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce a conditioned place preference and a striking dorsiflexion resembling the lordotic copulatory posture. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding: sexual receptivity is supplanted by aggression and a coincident decline in dopamine release in the nucleus accumbens. Together, these findings establish that Mrgprb4-lineage neurons initiate a skin-to-brain circuit encoding the rewarding quality of social touch.


Subject(s)
Dopamine , Touch , Mice , Male , Female , Animals , Dopamine/metabolism , Nucleus Accumbens/metabolism , Sensory Receptor Cells/metabolism , Skin/metabolism , Reward , Dopaminergic Neurons/metabolism , Optogenetics , Receptors, G-Protein-Coupled/metabolism
3.
Clin Obstet Gynecol ; 65(1): 195-202, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35045041

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 200 million people worldwide and has likely exposed millions of neonates to SARS-CoV-2 in utero. A large body of literature has examined the possibility of vertical transmission from pregnant women infected with SARS-CoV-2 to their neonates. In this chapter, we review mechanisms of-and evidence for-vertical transmission of SARS-CoV-2, including transplacental, through other biospecimens and breastfeeding, and discuss neonatal outcomes following in utero exposure. Based on the available literature, we conclude vertical transmission of SARS-CoV-2 is rare, and exposed neonates generally show favorable health outcomes.


Subject(s)
COVID-19 , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Pregnancy , SARS-CoV-2
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