Opioid Receptor Signaling Throughout Ontogeny: Shaping Neural and Behavioral Trajectories

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер 170, С. 106033 - 106033

Опубликована: Фев. 1, 2025

Язык: Английский

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A human iPSC-derived midbrain neural stem cell model of prenatal opioid exposure and withdrawal: A proof of concept study

PLoS ONE, Год журнала: 2025, Номер 20(4), С. e0319418 - e0319418

Опубликована: Апрель 1, 2025

A growing body of clinical literature has described neurodevelopmental delays in infants with chronic prenatal opioid exposure and withdrawal. Despite this, the mechanism how opioids impact developing brain remains unknown. Here, we developed an vitro model morphine withdrawal using healthy human induced pluripotent stem cell (iPSC)-derived midbrain neural progenitors monolayer. To optimize our model, identified that a longer induction regional patterning period increases expression canonical receptors mu kappa compared to shorter protocol ( OPRM1 , two-tailed t-test, p = 0.004; OPRK1 0.0003). Next, showed derived from iPSC also have scant toll-like receptor 4 (TLR4) expression, key player neonatal syndrome pathophysiology. During withdrawal, differentiating experience cyclic adenosine monophosphate overshoot exposed vehicle 0.0496) conditions 0.0136, 1-way ANOVA). Finally, alters proportions differentiated progenitor fates (2-way ANOVA, F 16.05, < 0.0001). Chronic increased nestin positive 0.0094), decreased neuronal nuclear antigen neurons (NEUN) 0.0047) those vehicle. Morphine glial fibrillary acidic protein cells astrocytic lineage 0.044), NEUN-positive 0.0001) only. Applications this paradigm include mechanistic studies underscoring fate commitments early neurodevelopment during

Язык: Английский

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The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice

Psychopharmacology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Язык: Английский

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The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 4, 2024

ABSTRACT Rationale Opioid use during pregnancy can lead to negative infant health outcomes, including neonatal opioid withdrawal syndrome (NOWS). NOWS comprises gastrointestinal, autonomic nervous system, and neurological dysfunction that manifest spontaneous withdrawal. Variability in severity necessitates a more individualized treatment approach. Ultrasonic vocalizations (USVs) mice are emitted isolation as stress response increased withdrawal, thus modeling affective state be utilized test new treatments. Objectives We sought identify the behavioral USV profile, brainstem transcriptomic adaptations, role of kappa receptors USVs Methods employed third trimester-approximate exposure model, where inbred FVB/NJ pups were injected twice-daily with morphine (10mg/kg, s.c.) or saline (0.9%, 20 ul/g, from postnatal day(P) 1 P14. This protocol induces reduced weight gain, hypothermia, thermal hyperalgesia, Results On P14, there emissions altered syllables an increase Complex 3 females (but not males). Brainstem bulk mRNA sequencing revealed upregulation receptor ( Oprk1) , which contributes withdrawal-induced dysphoria. The (KOR) antagonist, nor-BNI (30 mg/kg, s.c.), significantly females, but males Furthermore, KOR agonist, U50,488h (0.625 was sufficient on P10 (both sexes) P14 (females only) mice. Conclusions identified elevated syllable, 3, female-specific recruitment dynorphin/KOR system associated severity.

Язык: Английский

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The acoustic properties, syllable structure, and syllable sequences of ultrasonic vocalizations (USVs) during neonatal opioid withdrawal in FVB/N mouse substrains

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 7, 2024

Concomitant with the opioid epidemic, there has been a rise in pregnant women diagnosed use disorder and cases of infants born neonatal withdrawal syndrome (NOWS). NOWS refers to signs symptoms following cessation prenatal exposure that comprise neurological, gastrointestinal, autonomic system dysfunction. A critical indicator severity is excessive, high-pitched crying. However, evaluation is, large part, subjective, additional cry features may not be easily recognized during clinical assessment. Thus, need for more objective measures determine severity. We used third trimester-approximate paradigm model traits genetically similar inbred substrains FVB/N mice (NJ, NCrl, NHsd, NTac). Pups were injected twice daily from postnatal day 1 (P1) P14 morphine (10 mg/kg, s.c.) or saline (20 ml/g, s.c.). Because only very minor substrain differences spontaneous withdrawal-induced ultrasonic vocalization (USV) profiles, we collapsed across evaluate effects on USV properties. identified syllable sequences unique morphine-withdrawn saline-control pups P7 P14. also observed an effect acoustic properties USVs specific syllables Multiple correlated some type emission These data provide in-depth investigation mouse profiles mice.

Язык: Английский

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Chapter 8: The Role of Genetics in Neonatal Abstinence Syndrome

Seminars in Perinatology, Год журнала: 2024, Номер unknown, С. 152006 - 152006

Опубликована: Ноя. 1, 2024

Язык: Английский

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