Opioid receptor blockade throughout prenatal life confers long-term insensitivity to morphine and alters μ opioid receptors

Ian Zagon, Steven W. Tobias, Staci D. Hytrek, Patricia McLaughlin

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The influence of maternal opioid receptor blockade (50 mg/kg naltrexone, NTX) or saline (controls) throughout pregnancy on nociception and brain opioid receptor characteristics of rat offspring were examined; all animals were crossfostered to untreated mothers at birth. At 21 and 30 days, NTX- exposed pups weighed 8.2-24.3% more than controls, but both NTX and control groups were of similar body weights at 48, 60, and 80 days. Rats in the NTX and control groups displayed comparable baseline reactions to the hotplate. Morphine challenge tests and nociceptive measures revealed that NTX-subjected offspring examined at 21, 30, 48, and 60 days did not react to dosages that invoked 42-132% decreases from baseline levels in controls. Animals exposed prenatally to NTX were analgesic when injected with the opioid butorphanol or the nonopioid xylazine. The binding affinity (K(d)) and capacity (B(max)) of δ and κ opioid receptors were similar in NTX and control groups at 21 and 80 days. However, the B(max), but not the K(d), of μ opioid receptors was subnormal in NTX offspring by about 20% in contrast to control rats at 21 and 80 days. The results imply that the interactions of some endogenous opioids with opioid receptors during development are determinants of certain aspects of pain sensitivity as well as the density of particular opioid receptors in the postnatal period.

Original languageEnglish (US)
Pages (from-to)201-207
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume59
Issue number1
DOIs
StatePublished - Jan 1 1998

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Naltrexone
Opioid Receptors
Morphine
Control Groups
Opioid Analgesics
Rats
Animals
Rat control
Butorphanol
Xylazine
Nociception
Analgesics
Brain
Body Weight
Mothers
Parturition
Pain
Pregnancy

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

Cite this

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title = "Opioid receptor blockade throughout prenatal life confers long-term insensitivity to morphine and alters μ opioid receptors",
abstract = "The influence of maternal opioid receptor blockade (50 mg/kg naltrexone, NTX) or saline (controls) throughout pregnancy on nociception and brain opioid receptor characteristics of rat offspring were examined; all animals were crossfostered to untreated mothers at birth. At 21 and 30 days, NTX- exposed pups weighed 8.2-24.3{\%} more than controls, but both NTX and control groups were of similar body weights at 48, 60, and 80 days. Rats in the NTX and control groups displayed comparable baseline reactions to the hotplate. Morphine challenge tests and nociceptive measures revealed that NTX-subjected offspring examined at 21, 30, 48, and 60 days did not react to dosages that invoked 42-132{\%} decreases from baseline levels in controls. Animals exposed prenatally to NTX were analgesic when injected with the opioid butorphanol or the nonopioid xylazine. The binding affinity (K(d)) and capacity (B(max)) of δ and κ opioid receptors were similar in NTX and control groups at 21 and 80 days. However, the B(max), but not the K(d), of μ opioid receptors was subnormal in NTX offspring by about 20{\%} in contrast to control rats at 21 and 80 days. The results imply that the interactions of some endogenous opioids with opioid receptors during development are determinants of certain aspects of pain sensitivity as well as the density of particular opioid receptors in the postnatal period.",
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Opioid receptor blockade throughout prenatal life confers long-term insensitivity to morphine and alters μ opioid receptors. / Zagon, Ian; Tobias, Steven W.; Hytrek, Staci D.; McLaughlin, Patricia.

In: Pharmacology Biochemistry and Behavior, Vol. 59, No. 1, 01.01.1998, p. 201-207.

Research output: Contribution to journalArticle

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