Opiate Withdrawal in the Fetal Rat

Jones, Kathy L.; Barr, Gordon A.

doi:10.1016/s0091-3057(00)00209-4

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…The pup was then observed for a period of 20 min and behaviors recorded every 15 sec on a checklist (see Table I). The checklist was developed in previous experiments by observing and recording behaviors displayed by morphine-treated pups after systemic injection of naltrexone (Jones and Barr, 2000). When the observation period ended, rectal temperature was rerecorded and the pup was anesthetized and placed back into the litter.…”

Section: Behavioral Testingmentioning

confidence: 99%

“…Recently, the maturation of the physical signs of opiate withdrawal from the fetus (day 20 of gestation) through 42 days of postnatal life has been described (Jones and Barr, 1995;Windh et al, 1995;Jones and Barr, 2000). At all stages of development precipitated withdrawal was evidenced by a distinct and consistent behavioral syndrome, but the nature of that syndrome changed with age.…”

Section: Amygdalamentioning

confidence: 99%

“…At each level of development, precipitated withdrawal is evidenced by a distinct and consistent behavioral syndrome, but the nature of that syndrome changes with age. The classical withdrawal signs associated with adult opiate withdrawal do not appear until puberty (Jones and Barr, 1995;Windh et al, 1995;Jones and Barr, 2000). These data provide a model detailing the physical component of withdrawal at each different stage of development and thereby set the stage for the study of the anatomical substrates that mediate the opiate withdrawal syndrome in the developing animal.…”

Section: Introductionmentioning

confidence: 96%

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Injections of an opioid antagonist into the locus coeruleus and periaqueductal gray but not the amygdala precipitates morphine withdrawal in the 7‐day‐old rat

Jones

Barr

2000

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Section: Behavioral Testingmentioning

confidence: 99%

Section: Amygdalamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Injections of an opioid antagonist into the locus coeruleus and periaqueductal gray but not the amygdala precipitates morphine withdrawal in the 7‐day‐old rat

Jones

Barr

2000

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“…Naloxone administration rapidly induced withdrawal. Videos were time sampled at 15 min intervals and were scored for frequency of locomotion, rolling, curling, and stretching [29,30], by three trained raters blinded to the treatment condition.…”

Section: Methodsmentioning

confidence: 99%

A Novel Strategy for Attenuating Opioid Withdrawal in Neonates

et al. 2016

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The rate of Neonatal Abstinence Syndrome (NAS) has drastically increased over the past decade. The average hospital expense per NAS patient has tripled, while the number of babies born to opioid-dependent mothers has increased to 5 in 1000 births. Current treatment options are limited to opioid replacement and tapering. Consequently, we examined the efficacy of prenatal, low-dose and short-term vigabatrin (γ-vinyl GABA, GVG) exposure for attenuating these symptoms as well as the metabolic changes observed in the brains of these animals upon reaching adolescence. Pregnant Sprague-Dawley rats were treated in one of four ways: 1) saline; 2) morphine alone; 3) morphine+GVG at 25 mg/kg; 4) morphine+GVG at 50 mg/kg. Morphine was administered throughout gestation, while GVG administration occurred only during the last 5 days of gestation. On post-natal day 1, naloxone-induced withdrawal behaviours were recorded in order to obtain a gross behaviour score. Approximately 28 days following birth, 18FDG microPET scans were obtained on these same animals (Groups 1, 2, and 4). Morphine-treated neonates demonstrated significantly higher withdrawal scores than saline controls. However, GVG at 50 but not 25 mg/kg/day significantly attenuated them. Upon reaching adolescence, morphine treated animals showed regionally specific changes in 18FDG uptake. Again, prenatal GVG exposure blocked them. These data demonstrate that low-dose, short-term prenatal GVG administration blocks naloxone-induced withdrawal in neonates. Taken together, these preliminary findings suggest that GVG may provide an alternative and long-lasting pharmacologic approach for the management of neonatal and adolescent symptoms associated with NAS.

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“…Opiate withdrawal in fetal sheep activates the sympathetic nervous system and alters blood pressure, blood oxygen content, and causes meconium staining (Cohen et al, 1980;Umans and Szeto, 1985). Increased motoric activity after prenatal opiate withdrawal has also been reported in externalized rodent fetuses (Kirby and Holtzman, 1982;Jones and Barr, 2000). However, it is unclear whether other aspects of opiate withdrawal documented in the adult, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis (for review, see Pechnick, 1993) occur in the immature subject as well.…”

mentioning

confidence: 99%

Prenatal Opiate Withdrawal Activates the Chick Embryo Hypothalamic-Pituitary-Adrenal Axis and Dilates Vitelline Blood Vessels via Serotonin₂ Receptors

Schrott¹,

Baumgart²,

Zhang³

et al. 2002

J Pharmacol Exp Ther

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Opiate withdrawal during pregnancy may occur because of voluntary or forced detoxification, or from rapid cycling associated with exposure to short-acting "street" opiates. Thus, animal modeling of prenatal withdrawal and development of potential therapeutic interventions is important. Direct developmental effects of opiates and/or withdrawal can be studied using a chick model. In ovo administration of the long-acting opiate N-desmethyl-l-␣-noracetylmethadol (NLAAM) induces opiate dependence in the chick embryo. We examined activation of the hypothalamic-pituitary-adrenal (HPA) axis (assessed via serum corticosterone) and hemodynamic changes (assessed as changes in apparent diameter of vitelline (extraembryonic) blood vessels) after chronic NLAAM exposure and naloxone (Nx)-precipitated withdrawal during late stages of embryogenesis. Nx-precipitated withdrawal increased corticosterone 2-to 4.5-fold and diameters of vitelline blood vessels by 15 to 45%. NLAAM exposure itself did not effect these measures. In a second set of experiments, isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, was injected into eggs with embryos. IBMX similarly increased corticosterone and vitelline vessel diameter, with a similar time course and response magnitude. Previous studies found that serotonin 2 (5-HT 2 ) receptors were involved in other withdrawal manifestations, so we determined whether they were likewise involved. Pretreatment with the 5-HT 2 antagonist ritanserin completely blocked HPA axis activation and vasodilation associated with both Nx-precipitated withdrawal and IBMX administration. This indicates that 5-HT 2 receptors, directly or indirectly, mediate these withdrawal manifestations in the chick embryo.

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Opiate Withdrawal in the Fetal Rat

Cited by 15 publications

References 19 publications

Injections of an opioid antagonist into the locus coeruleus and periaqueductal gray but not the amygdala precipitates morphine withdrawal in the 7‐day‐old rat

Injections of an opioid antagonist into the locus coeruleus and periaqueductal gray but not the amygdala precipitates morphine withdrawal in the 7‐day‐old rat

A Novel Strategy for Attenuating Opioid Withdrawal in Neonates

Prenatal Opiate Withdrawal Activates the Chick Embryo Hypothalamic-Pituitary-Adrenal Axis and Dilates Vitelline Blood Vessels via Serotonin₂ Receptors

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Opiate Withdrawal in the Fetal Rat

Cited by 15 publications

References 19 publications

Injections of an opioid antagonist into the locus coeruleus and periaqueductal gray but not the amygdala precipitates morphine withdrawal in the 7‐day‐old rat

Injections of an opioid antagonist into the locus coeruleus and periaqueductal gray but not the amygdala precipitates morphine withdrawal in the 7‐day‐old rat

A Novel Strategy for Attenuating Opioid Withdrawal in Neonates

Prenatal Opiate Withdrawal Activates the Chick Embryo Hypothalamic-Pituitary-Adrenal Axis and Dilates Vitelline Blood Vessels via Serotonin2 Receptors

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Prenatal Opiate Withdrawal Activates the Chick Embryo Hypothalamic-Pituitary-Adrenal Axis and Dilates Vitelline Blood Vessels via Serotonin₂ Receptors