Abstract
Prenatal exposure to morphine causes altered glutamatergic neurotransmission, which plays an important pathophysiological role for neurobiological basis of opiate-mediated behaviors in such offspring. However, it is still not clear whether such alteration involves gene expression of ionotropic glutamate receptor subunits. In this study, we further studied whether prenatal morphine exposure resulted in long-term changes in the gene expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, N-methyl-d-aspartate (NMDA) receptor, and postsynaptic density 95 in the mesocorticolimbic area (an essential integration circuitry for drug craving behavior), nucleus accumbens (NAc), ventral tegmental area (VTA), and prefrontal cortex (PFC), of rat offspring from morphine-addicted mothers. Experimental results showed that prenatal morphine exposure led to a persistent downregulation of gene expression in the AMPA and NMDA receptor subunit, with a differential manner of decreased magnitudes, at the age of postnatal days 14 (P14) and P30. However, in PFC, the gene expression of the AMPA receptor subunit was not synchronized in observed rat offspring subjected to prenatal morphine exposure. An upregulation of gene expression in the AMPA receptor subunit 3 (GluR3) was persistently observed at P14 and P30. Furthermore, the gene expressions of PSD-95 in NAc, VTA, and PFC were all decreased concurrently. Collectively, the results suggest that prenatal exposure to morphine may initiate molecular mechanisms leading to a long-lasting, differential alteration in gene expression of the inotropic glutamate receptor subunit and PSD-95 in the mesocorticolimbic circuitry in rat offspring. This study raises a possibility in which differential changes in gene expression with a long-lasting manner may play a role for the development of nearly permanent changes in opiate-mediated behaviors, at least in part for the neurobiological pathogenesis in offspring.
Highlights
Maternal drug addiction is a worldwide growing issue; it is associated with increased perinatal mortality and morbidity in children
At the same age, the relative mRNA levels of the amino-3-hydroxy-5-methyl-4isoxazolepropionic acid receptor (AMPAR) subunit (GluR14) within nucleus accumbens (NAc) were all markedly decreased in the prenatal morphine group at postnatal days 14 (P14) (P < 0.05, n = 8 animals, Figure 1) and postnatal days 30 (P30) (P < 0.05, n = 8 animals, Figure 1), as compared with the vehicle-control group
The greatest decrease in downregulation of gene expression of GluR2 and GluR4 was observed at P14 but not at P30
Summary
Maternal drug addiction is a worldwide growing issue; it is associated with increased perinatal mortality and morbidity in children. Using morphine in pregnancy might cause spontaneous abortion, preterm delivery, multiple congenital anomaly, and neonatal abstinence syndrome [1]. Neonatal abstinence syndrome is a complex disorder that mainly involved the central and autonomous nervous system and gastrointestinal system. Neonatal abstinence syndrome might present symptoms with mild irritable tremors, high pitch crying, fever, and seizure [1]. Prenatal drug exposure causes perinatal effect and might lead to long-term cognitive impairment and increased prevalence. Environment factors might be important for developing later neurological negative consequences, the alternated function and structure of central nervous system in these prenatal-drug-exposure neonates might play an important role
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