The effect of morphine administration on GluN3B NMDA receptor subunit mRNA expression in rat brain.

Opioid addiction is critically dependent on the activation of N­methyl­D­aspartate (NMDA) receptors, which are widely found in the mesocorticolimbic system. Meanwhile, opioid addiction may affect the expression level of NMDA receptor subunits. The existence of GluN3 subunits in the NMDA receptor's tetramer structure reduces the excitatory current of the receptor channel. We evaluated the changes in the mRNA expression pattern of the GluN3B subunit of the NMDA receptor in rat brains following acute and chronic exposure to morphine. Chronic, escalating intraperitoneal doses of morphine or saline were administered twice daily to male Wistar rats for six days. Two other groups were injected with a single acute dose of morphine or saline. The mRNA level of the GluN3B subunit of the NMDA receptor in the striatum, hippocampus, and nucleus accumbens (NAc) was measured by real­time PCR. mRNA expression of the GluN3B subunit was considerably augmented (3.15 fold) in the NAc of animals chronically treated with morphine compared to the control group. The difference between rats that were chronically administered morphine and control rats was not statistically significant for other evaluated brain areas. In rats acutely treated with morphine, no significant differences were found for GluN3B subunit expression in the examined brain regions compared to the control group. It was concluded that chronic exposure to morphine notably increased the GluN3B subunit of the NMDA receptor in NAc. The extent of the impact of this finding on opioid addiction and its features requires further evaluation in future studies.

Pre-mating administration of theophylline could prevent the transgenerational effects of maternal morphine dependence on offspring anxiety behavior: The role of dopamine receptors.

Opioid addiction causes some molecular alterations in the brain reward pathway, such as changes in gene expression that may be transferred to the next generation via epigenetic mechanisms such as histone acetylation. This study aimed to evaluate the effect of theophylline as an HDAC (Histone deacetylases) activator on D1 and D2 dopamine receptor expression in the nucleus accumbens (NAc) and anxiety behavior in the offspring of morphine-dependent female rats. Female rats were exposed to escalating doses of morphine for six days and were then treated with theophylline (20 mg/kg) or saline for 10 days before mating with normal male rats. Male and female offspring were tested for anxiety behavior using an elevated plus maze apparatus. Besides, the expression of D1 and D2 dopamine receptors in the NAc was evaluated by real-time PCR (polymerase chain reaction). Results showed that offspring of morphine-dependent female rats had increased expression of both D1 and D2 receptors in the NAc, as well as decreased anxiety behavior, compared to control offspring. However, the mentioned effects were returned to normal levels in the offspring whose morphine-dependent mothers had received theophylline for 10 days before mating. It is concluded that theophylline may be therapeutically effective in minimizing the adverse consequences of maternal morphine dependence on offspring behavior by restoring normal dopamine receptor expression levels and modulating anxiety. To completely comprehend the underlying mechanisms of this phenomenon, more research is required.