Negative affectivity drivers of impulsivity in opioid use disorder
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Outpatient tapering of buprenorphine in opioid use disorder pregnancies may improve neonatal outcomes
The main objective of the study was to compare neonatal outcomes: the incidence of NOWS, length of hospital stay (LOS), admission to neonatal intensive care (NICU), birth weight, treatment with morphine, and head circumference between newborns of mothers who had tapering of buprenorphine (T group) during pregnancy to non-tapering of buprenorphine (NT group).
The dopaminergic effects of esketamine are mediated by a dual mechanism involving glutamate and opioid receptors
Esketamine represents a new class of drugs for treating mood disorders. Unlike traditional monoaminergic-based therapies, esketamine primarily targets N-methyl-D-aspartate receptors (NMDAR). However, esketamine is a complex drug with low affinity for NMDAR and can also bind to other targets, such as opioid receptors. Its precise mechanism of action for its antidepressant properties remains debated, as does its potential for misuse. A key component at the intersection of mood and reward processing is the dopaminergic system. In this study, we evaluated the effects of esketamine in locomotion, anxiety tests and operant responding and we used in vivo fiber photometry to explore the neurochemical effects of esketamine in the nucleus accumbens of mice. Our findings demonstrated multifaceted effects of esketamine on neurotransmitter dynamics. In freely behaving mice, esketamine increased locomotion and increased extracellular dopamine tone -by impairing dopamine clearance rather than promoting dopamine release- while decreasing glutamatergic activity. However, it decreased dopamine spontaneous release event frequency and impaired reward-evoked dopamine release, leading to a reduction in operant responding rates. These dopaminergic effects were partially, and conditionally, blocked by the opioid antagonist naloxone and required glutamatergic input. In summary, our study reveals a complex interaction between neurotransmitter systems, suggesting that the neurochemical effects of esketamine are both circuit- and state-dependent.
“Is eat, sleep, console the key to safer and faster discharge for newborns with neonatal opioid withdrawal syndrome?”
Manuscript Citation Young, L. W., Ounpraseuth, S. T., Merhar, S. L., Hu, Z., Simon, A. E., Bremer, A. A., … & Devlin, L. A. (2023).…
Coastal wetland resilience through local, regional and global conservation
Coastal wetlands, including tidal marshes, mangrove forests and tidal flats, support the livelihoods of millions of people. Understanding the resilience of coastal wetlands to the increasing number and intensity of anthropogenic threats (such as habitat conversion, pollution, fishing and climate change) can inform what conservation actions will be effective. In this Review, we synthesize anthropogenic threats to coastal wetlands and their resilience through the lens of scale. Over decades and centuries, anthropogenic threats have unfolded across local, regional and global scales, reducing both the extent and quality of coastal wetlands. The resilience of existing coastal wetlands is driven by their quality, which is modulated by both physical conditions (such as sediment supply) and ecological conditions (such as species interactions operating from local through to global scales). Protection and restoration efforts, however, are often localized and focus on the extent of coastal wetlands. The future of coastal wetlands will depend on an improved understanding of their resilience, and on society’s actions to enhance both their extent and quality across different scales.
Genome-wide association study reveals multiple loci for nociception and opioid consumption behaviors associated with heroin vulnerability in outbred rats
The increased prevalence of opioid use disorder (OUD) makes it imperative to disentangle the biological mechanisms contributing to individual differences in OUD vulnerability. OUD shows strong heritability, however genetic variants contributing to vulnerability remain poorly defined. We performed a genome-wide association study using over 850 male and female heterogeneous stock (HS) rats to identify genes underlying behaviors associated with OUD such as nociception, as well as heroin-taking, extinction and seeking behaviors. By using an animal model of OUD, we were able to identify genetic variants associated with distinct OUD behaviors while maintaining a uniform environment, an experimental design not easily achieved in humans. Furthermore, we used a novel non-linear network-based clustering approach to characterize rats based on OUD vulnerability to assess genetic variants associated with OUD susceptibility. Our findings confirm the heritability of several OUD-like behaviors, including OUD susceptibility. Additionally, several genetic variants associated with nociceptive threshold prior to heroin experience, heroin consumption, escalation of intake, and motivation to obtain heroin were identified. Tom1, a microglial component, was implicated for nociception. Several genes involved in dopaminergic signaling, neuroplasticity and substance use disorders, including Brwd1, Pcp4, Phb1l2 and Mmp15 were implicated for the heroin traits. Additionally, an OUD vulnerable phenotype was associated with genetic variants for consumption and break point, suggesting a specific genetic contribution for OUD-like traits contributing to vulnerability. Together, these findings identify novel genetic markers related to the susceptibility to OUD-relevant behaviors in HS rats.
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