Elsevier

Neurotoxicology and Teratology

Volume 14, Issue 4, July–August 1992, Pages 265-271
Neurotoxicology and Teratology

Article
Chronic prenatal methadone exposure alters central opioid μ-receptor affinity in both fetal and maternal brain

https://doi.org/10.1016/0892-0362(92)90006-VGet rights and content

Abstract

The effects of chronic prenatal methadone exposure (6.3–9.0 mg/kg/day) via osmotic minipumps to pregnant dams on fetal and maternal brain opioid μ-receptors were assessed on gestation day 20 and day 7 postnatally. By using the 3H-DAMGO binding assay, it was shown that chronic methadone treatment (gestation days 7–20) did not affect μ-receptor capacity in both fetal and maternal brains during gestation day 20, nor when tested 7 days after delivery. However, this chronic exposure decreased μ-receptor affinity in both fetal and maternal brain homogenates when determined on day 20 of pregnancy. Scatchard analysis of binding data in both tissues indicated that the methadone-induced increase in KD returned to control values when tested 7 days after delivery. The change in μ-receptor affinity was not due to competition between 3H-DAMGO and residual methadone. Extensive washing of the brain homogenates failed to alter the affinity of the receptor but decreased the concentration of the residual methadone. This decrease in receptor affinity was also observed in extensively washed brain tissue from female adult rats treated acutely with methadone (9.0 mg/kg, IP) or when brain homogenates were exposed to methadone (50 ng/ml) in vitro. Thus, these data suggest that methadone alters μ-receptor affinity by some unknown mechanism.

References (49)

  • V. Höllt et al.

    Comparison of in vivo and in vitro parameters of opiate receptor binding in mouse and tolerant/dependent rodents

    Life Sci.

    (1975)
  • M.L. Kirby et al.

    Levorphanol-sensitive 3H-naloxone binding in developing brainstem following prenatal morphine exposure

    Neurosci. Lett.

    (1983)
  • F.M. Leslie et al.

    Differential appearance of opiate receptor subtypes in neonatal rat brain

    Life Sci.

    (1982)
  • D.C. Perry et al.

    In vivo binding of 3H-etorphine in morphine dependent rats

    Life Sci.

    (1982)
  • N.F. Rogers et al.

    Morphine-induced opioid receptor down-regulation in intact rat brain cells

    Eur. J. Pharmacol.

    (1986)
  • S.P. Sivam et al.

    Alteration of synaptic high and low affinity opiate binding sites after acute and chronic morphine administration in mice

    Prog. Neuropsychopharmacolol. Biol. Psychiat.

    (1982)
  • R.J. Tallarida et al.

    Estimation of dissociation constant of naloxone in the naive and morphine-tolerant guinea pig isolated ileum: Analysis by the constrained Schild plot

    Life Sci.

    (1982)
  • A. Tavani et al.

    Differential postnatal development of μ-, δ- and κ-opioid binding sites in mouse brain

    Develop. Brain Res.

    (1985)
  • A. Tempel et al.

    Morphine-induced downregulation of μ-opioid receptors in neonatal rat brain

    Develop. Brain Res.

    (1988)
  • D. Tsang et al.

    Ontogenesis of opiate binding sites and radioimmunoassayable β-endorphin and enkephalin in regions of rat brain

    Dev. Brain Res.

    (1982)
  • J.R. Unnerstall et al.

    Ontogeny of opiate binding sites in the hippocampus, olfactory bulb and other regions of the rat forebrain by autoradiographic methods

    Dev. Brain Res.

    (1983)
  • A. Valette et al.

    Specific binding for opiate-like drugs in the placenta

    Biochem. Pharmacol.

    (1980)
  • M. Wohltmann et al.

    Differential postnatal development of mu and delta opiate receptors

    Dev. Brain Res.

    (1982)
  • I.S. Zagon et al.

    Perinatal methadone exposure and its influence on the behavioral ontogeny in rats

    Pharmacol. Biochem. Behav.

    (1978)
  • Cited by (15)

    • Effects of opioids on the parental brain in health and disease

      2019, Frontiers in Neuroendocrinology
      Citation Excerpt :

      For mothers with OUD, adaptative parenting behaviors depend on their perceived parenting stress (Suchman and Luthar, 2001), which depends on how well they can emotional attune to the child’s psychological needs (Borelli et al., 2012). It is well known that gestational opioid exposure results in alterations in opioid receptor binding and functionality in dams during pregnancy and the early postpartum (Hou et al., 2004; Darmani et al., 1992), however only a few comparative studies have investigated the effects of opioids on a parental brain compared to a virgin or non-postpartum brain. Though changes in pharmacokinetics and thus plasma and tissue distribution of opioids are well established during pregnancy (Shah et al., 1976), the effects of these changes on the maternal brain are not well documented.

    • Child neuroanatomical, neurocognitive, and visual acuity outcomes with maternal opioid and polysubstance detoxification

      2015, Pediatric Neurology
      Citation Excerpt :

      However, the lower visual acuity in part observed in the risk group gives reason for concern because vision problems have repeatedly been shown in opioid-exposed children.43,44 Animal studies have shown detrimental effects of prenatal methadone on neurotransmitters and mu-receptor affinity45,46 that may have adverse effects on vision. In a recent report, summed raw scores for picture completion and vocabulary did not deviate across a group of OMT- and nicotine-exposed 4 year olds relative to a comparison group.47

    View all citing articles on Scopus
    1

    Present address: Department of Pharmacology, Kirksville College of Osteopathic Medicine, Kirksville, MO 63501.

    View full text