Chronic in utero morphine exposure alters mu-agonist-stimulated [35S]-GTPgammaS binding in neonatal and juvenile guinea pig brainstem regions associated with breathing control.
Narcotic analgesics act acutely upon opioid receptors in the brainstem to depress respiration in neonates, whereas withdrawal from chronic in utero exposure to morphine is associated with hyperventilation in the newborn. Because of the association between breathing and exposure to exogenous opioids, opioid-stimulated [35S]-guanylyl-5'-O-(gamma-thio)-triphosphate ([35S]-GTPgammaS) binding was examined in respiratory control areas of the brainstem in 3-, 7-, and 14-day-old guinea pigs who were exposed during the last 2 weeks of gestation by maternal subcutaneous injections of 7.5 mg/kg of morphine or an equal volume of saline twice daily. Ten micromolar D-ala(2), MePhe(4), Gly(ol)(5)-enkephalin (DAMGO), a mu-specific opioid receptor agonist, stimulated [35S]-GTPgammaS binding in the caudal and rostral ventral respiratory groups (cVRG and rVRG), nucleus tractus solitarius (NTS), and the parabrachial nucleus (PB). There were no statistically significant age-related changes in DAMGO-stimulated binding for any of the respiratory areas. However, morphine-exposed animals had decreased DAMGO-stimulated [35S]-GTPgammaS binding in these brainstem areas compared to saline-exposed animals. We hypothesize that this morphine-induced decrease in DAMGO activation of the mu-opioid receptor may be a partial explanation for the hyperventilation observed during neonatal morphine withdrawal.
Matsuda
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AY
Department of Physiology and Pharmacology, Oregon Health and Science University, L-334, 3181 Southwest Sam Jackson Park Road, Portland, OR 97201-3098, USA.
Olsen
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GD
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D006168:Guinea Pigs; D008098:Litter Size; D009021:Morphine Dependence; D011247:Pregnancy; D011248:Pregnancy Complications / Q000523:psychology*; D011297:Prenatal Exposure Delayed Effects; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012143:Respiratory Physiological Phenomena; D013462:Sulfur Radioisotopes
D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate)