Prenatal administration of methadone using the osmotic minipump: Effects on maternal and offspring toxicity, growth, and behavior in the rat

Donald E. Hutchings, Ann Zmitrovich, Stephen C. Brake, Daniel Malowany, Sarah Church, Thomas J. Nero

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Two doses of methadone were administered by osmotic minipump from day 8 of gestation through parturition. A pair-fed control group received saline via minipump and was allowed to eat and drink only the amount consumed by the high dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Naloxone challenge of the dams after parturition showed that drug treatment produced physical dependence. Methadone treatment reduced maternal weight gain but had no effect on either the frequency of resorptions or birthweight. Both doses of methadone increased perinatal mortality but only the high dose produced a decrement in postnatal growth. To examine the effects of methadone on the rest-activity cycle of the offspring, groups of three littermates from each of the treated and control groups were tested for an 8 h observation period on electronic activity monitors at 22 days of age. No behavioral effects were observed for either control group or the low dose methadone group. The high dose methadone offspring, however, spent less time resting, showed disrupted rhythmicity, and poor state regulation. These findings are discussed in relation to earlier studies using once per day methadone administration as well as clinical descriptions of infants undergoing opiate abstinence.

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalNeurotoxicology and Teratology
Volume14
Issue number1
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • Methadone
  • Opioid abstinence
  • Osmotic minipump
  • Prenatal
  • Rat
  • Rest-Activity Cycle

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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