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Aim:To characterize the effect of combined pre-and postnatal morphine exposureon N-methyl-D-aspartate receptor(NMDA)receptor signaling in hippocampalneurons of the offspring of morphine-addicted female rats.Methods:Culturedhippocampal neurons and synaptosomes were prepared from neonatal and 2-week-old offspring,respectively,of control or morphine-addicted female rats.Theincrease in the cytosolic Ca~(2+)concentration([Ca~(2+)]_i)of cultured cells was mea-sured using Fura-2,and glutamate release from synaptosomes was measuredenzymatically.Results:Both glutamate and NMDA caused a dose-dependentincrease in the[Ca~(2+)]_i.The nitric oxide(NO)donor,S-nitrosoglutathione(GSNO),but not 3-morpholinosydnonimine,sodium nitroprusside,and S-nitroso-N-acetylpenicillamine,also induced a[Ca~(2+)]_i increase.GSNO and glutathione causeda dose-dependent increase in the[Ca~(2+)]_i with respective EC_(50)values of 56 and 414μmol/L.Both effects were inhibited by Mg~(2+)or an NMDA receptor antagonistand were unaffected by the presence of a glutamate scavenger.The other glu-tathione derivatives,oxidized glutathione,S-methylglutathione,S-ethylglutathione,S-propylglutathione,and S-butylglutathione,the dipeptides,Glu-Cys and Cys-Gly,and the antioxidants,dithiothreitol and mercaptoethanol,failed to induce a[Ca~(2+)]_i increase.In addition,glutathione caused a dose-dependent increase inglutamate release from synaptosomes.The maximal responses and the EC_(50)val-ues for the glutamate-,NMDA-,GSNO-,and glutathione-induced[Ca~(2+)]_i increasesand the glutathione-induced glutamate release were indistinguishable in the neu-rons of the offspring from control and morphine-addicted female rats.Conclusion:GSNO and glutathione act as NMDA receptor agonists and,in contrast to hippoc-ampal brain slice,combined pre-and postnatal morphine exposure does not modu-late NMDA receptor signaling in the cultured hippocampal neurons.
Aim: To characterize the effect of combined pre-and postnatal morphine exposure on N-methyl-D-aspartate receptor (NMDA) receptor signaling in hippocampal neurones of the offspring of morphine-addicted female rats. Methods: Cultured hippocampal neurons and synaptosomes were prepared from neonatal and 2-week-old offspring, respectively, of control or morphine-addicted female rats. The increment in the cytosolic Ca 2+ concentration ([Ca 2+] i) of cultured cells was mea- sured using Fura- 2, and glutamate release from synaptosomes was measuredenzymatically. Results: Both glutamate and NMDA caused a dose-dependent increase in the [Ca ~ (2 +)] _i.The nitric oxide (NO) donor, S-nitrosoglutathione (GSNO), but not 3-morpholinosydnonimine, sodium nitroprusside, and S-nitroso-N-acetylpenicillamine, also induced a [Ca ~ (2 +)] _i increase.GSNO and glutathione causeda dose-dependent increase in the [Ca ~ (2 +)] _i with Each EC_ (50) values of 56 and 414 μmol / L. Butoth effects were inhibited by Mg ~ (2+) or an NMDA receptor antagonistand were unaffected by the presence of a glutamate scavenger. the other glu-tathione derivatives, oxidized glutathione, S-methylglutathione, S-ethylglutathione, S-propylglutathione, and S-butylglutathione, the dipeptides, Glu- Cys and Cys-Gly, , dithiothreitol and mercaptoethanol, failed to induce a [Ca ~ (2 +)] _ i increase. addition, glutathione caused a dose-dependent increase inglutamate release from synaptosomes. The maximal responses and the EC_ (50) val-ues for the glutamate -, NMDA-, GSNO-, and glutathione-induced [Ca ~ (2 +)] _i increases and the glutathione-induced glutamate release were indistinguishable in the neu-rons of the offspring from control and morphine-addicted female rats. Conlusion: GSNO and glutathione act as NMDA receptor agonists and, in contrast to hippocampal brain slices, combined pre-and postnatal morphine exposure does not modu-late NMDA receptor signaling in the cultured hippocampal neurons.