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

Pharmacology, Biochemistry, and Behavior
I S ZagonP J McLaughlin

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 (Kd) and capacity (Bmax) of delta and kappa opioid receptors were similar in NTX and control groups at 21 and 80 days. However, the Bmax, but not the Kd, of mu 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 developm...Continue Reading

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Citations

Oct 16, 1999·Brain Research·I S ZagonP J McLaughlin
Jul 31, 2013·Annals of Epidemiology·Richard A EpsteinWilliam O Cooper
Jun 19, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Emily J RossGregg D Stanwood
Jan 12, 2019·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Florence ThibautKim Yonkers
Nov 10, 2017·Expert Opinion on Drug Safety·Mariangela AntonelliGiovanni Addolorato
Mar 10, 2015·Harvard Review of Psychiatry·Jeffrey DeVidoRoger D Weiss
Dec 20, 2002·Developmental Biology·Joshua F Nitsche, John E Pintar

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