Prenatal Withdrawal from Opiates Interferes with Hatching of Otherwise Viable Chick Fetuses

Kuwahara,; Sparber, Sheldon B.

doi:10.1126/science.7195069

Cited by 27 publications

(7 citation statements)

References 18 publications

(4 reference statements)

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“…Consequently, disruption of the natural course of cellular events occurring during this early period may lead to later functional disorders. The similarity of agonist-antagonist effects on adenylate cyclase during early embryonic development may be of functional signifiLcance in partially explaining the effects of prenatal opiate withdrawal reported in the rat (11) and the chick (12). These investigators were able to show that opiate withdrawal in utero increased neonatal morbidity in the rat and that withdrawal from opiates interfered with hatching in otherwise viable chicken fetuses.…”

Section: Discussionmentioning

confidence: 94%

“…7 and 8). In addition, the interaction between the opiate antagonist naloxone and the adenylate cyclase system is important because opiate antagonists (naltrexone) are currently being used in the treatment ofopiate addiction (9, 10) and a toxic effect on the embryo has been suggested (11,12). These investigators showed, in both the chicken and the rat, that administration of naloxone to morphine-dependent embryos increased their morbidity as compared with low doses of morphine alone.…”

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confidence: 99%

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An unconventional response of adenylate cyclase to morphine and naloxone in the chicken during early development.

Sakellaridis¹,

Vernadakis²

1986

Proc. Natl. Acad. Sci. U.S.A.

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The developmental profile of basal, NaF-and forskolin-stimulated adenylate cyclase [ATP-pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity was established throughout the 21-day embryonic age of the chicken. The highest activities were observed from day 6 to day 8. Morphine inhibited NaF-and forskolin-stimulated brain adenylate cyclase activities only at days 6-8. The inhibition was not reversed by the antagonist naloxone, which also inhibited the enzyme during the same embryonic period and had no inhibitory effect thereafter. Thus, this action of morphine is not mediated through the conventional opiate receptor-adenylate cyclase system. We propose that the temporal specificity of this effect of morphine may play a role in the development of prenatal opiate effects.The adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] enzyme system (1, 2) plays a pivotal role in cell-cell interactions and is the membranous target of several hormones and neurotransmitters. In addition, the adenylate cyclase system is important throughout the phylogenetic scale beginning with unicellular organisms up to the elaborate receptor systems (3). Thus, the embryo that begins as a unicellular zygote might also be expected to utilize the adenylate cyclase system throughout development.The first goal in this study was to determine the presence and functional state of adenylate cyclase and its components in the chicken embryo, and we report here its presence throughout embryonic development up to hatching, with maximal activity from day 6 to day 8. The second goal was to evaluate the functional relationship between the enzyme system and exogenously administered opiates, morphine and naloxone, in order to find out how the opiate receptors, present early in the chicken embryo, interacted with the cyclase system. Previous studies from this laboratory have shown the presence of opiate receptors in the chicken at an embryonic age as early as day 4. Moreover, we found that an analogue of methadone, 1-a-acetylmethadol-HCL, greatly affected the binding and affinity of [3H]etorphine both in ovo and in culture (4-6). The effects of opiates in early growth phenomena are of particular clinical relevance in view of the fact that infants born to mothers addicted to opiates exhibit dependency to the narcotic and develop symptoms of withdrawal at birth (for reviews, see refs. 7 and 8). In addition, the interaction between the opiate antagonist naloxone and the adenylate cyclase system is important because opiate antagonists (naltrexone) are currently being used in the treatment ofopiate addiction (9, 10) and a toxic effect on the embryo has been suggested (11,12). These investigators showed, in both the chicken and the rat, that administration of naloxone to morphine-dependent embryos increased their morbidity as compared with low doses of morphine alone. They attributed these effects to prenatal withdrawal of the addicted embryo.Moreover, several investigators have established the relationship between the opiates and the adenylat...

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

An unconventional response of adenylate cyclase to morphine and naloxone in the chicken during early development.

Sakellaridis¹,

Vernadakis²

1986

Proc. Natl. Acad. Sci. U.S.A.

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“…Opiate withdrawal is not recommended during pregnancy unless the mother refuses opiate maintenance therapy due to increased likelihood of relapse (ACOG Committee, 2012). Animal studies have demonstrated in utero withdrawal to increase fetal activity and perinatal mortality (Kirby and Holtzmann, 1982;Kuwahara and Sparber, 1981;Lichtblau and Sparber, 1981).…”

Section: Opiate Maintenance Therapiesmentioning

confidence: 99%

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Ross

Graham

Money

et al. 2014

Neuropsychopharmacol

327

241

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Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.

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“…It is a general assumption that perinatal morbidity is caused by the development of narcotic dependence in the fetus as a direct result of placental transport of the drug. However, these difficulties may have their origin in utero as the result of the fetus experiencing withdrawal during gestation (Kuwahara & Sparber, 1981; Lichtblau & Sparber, 1981). At birth, the newborn infant continues to experience withdrawal due to the absence of the drug.…”

mentioning

confidence: 99%

Ontogeny of morphine withdrawal in the rat.

Jones¹,

Barr²

1995

Behavioral Neuroscience

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The present studies examined behavioral changes during precipitated morphine withdrawal in 7- to 42-day-old rat pups. One group of rats was injected with morphine sulfate (10.0 mg/kg) twice daily for 6.5 days. Another group of 7-day-old rats received a lower dose of morphine (3.0 mg/kg). Controls were saline injected or untreated litters (7-day-old pups only). On Day 7, a target pup was injected with saline or naltrexone (0.3-10.0 mg/kg). Preweaning pups were observed in a warm chamber with the litter. Forty-two-day-old rats were tested individually. Morphine-treated pups tested with naltrexone showed significant alterations in behavior that varied at different ages. For example, rolling, stretching, and head and paw moves were observed at the younger ages, whereas burrowing, diarrhea, jumps, teeth chatter, and wet dog shakes occurred in the older rats. These data indicate that morphine-abstinent rats demonstrate withdrawal signs that are within the developmental repertoire of the rat.

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Prenatal Withdrawal from Opiates Interferes with Hatching of Otherwise Viable Chick Fetuses

Cited by 27 publications

References 18 publications

An unconventional response of adenylate cyclase to morphine and naloxone in the chicken during early development.

An unconventional response of adenylate cyclase to morphine and naloxone in the chicken during early development.

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Ontogeny of morphine withdrawal in the rat.

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