Research reportChronic exposure to morphine decreases the expression of EAAT3 via opioid receptors in hippocampal neurons

- Morphine decreases EAAT3 expression in hippocampal neurons.
- Morphine increases the extracellular Glu concentration of hippocampal neurons.
- The morphine-dependent down-regulation of EAAT3 may be mediated by MOR and DOR.
- KOR may not contribute to the morphine-dependent down-regulation of EAAT3.

Alterations in glutamate transporter expression are closely related to opiate addition behavior, but the role of opioid receptors is unclear. In this study, we used primary cultures of hippocampal neurons from neonatal rats to study the effects of chronic exposure to morphine on excitatory amino acid transporter 3 (EAAT3) expression and the roles of µ opioid receptor (MOR), δ opioid receptor (DOR), and κ opioid receptor (KOR) in the morphine-dependent alterations in EAAT3 expression. The results showed that the EAAT3 protein and mRNA expression levels decreased significantly after chronic exposure to morphine (10 μmol/L) for 48 h, whereas the concentration of extracellular glutamate increased. In addition, we found that both the MOR inhibitor CTOP and the DOR inhibitor naltrindole could reverse the decreased expression of EAAT3 after exposure to morphine, whereas the MOR activator DAMGO and the DOR activator DPDPE significantly decreased EAAT3 expression. The KOR inhibitor had no effect on the expression of EAAT3, whereas its activator increased EAAT3 expression. These results suggest that the down-regulation of morphine-dependent EAAT3 expression in primary rat hippocampal cultures may be mediated by MOR and DOR and that KOR may not contribute significantly to this effect.This article is part of a Special Issue entitled SI:Addiction circuits.