Morphine causes a delayed increase in glutamate receptor functioning in the nucleus accumbens core

Enhanced excitatory neurotransmission in the mesocorticolimbic system may contribute to the persistence of addiction behaviour. Here, we demonstrated that glutamate-, N-methyl-d-aspartate (NMDA)- and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-induced [3H]-γ-aminobutyric acid (GABA) release from superfused rat nucleus accumbens core slices is profoundly enhanced 3 weeks, but not 3 days, after a single s.c. morphine injection. This delayed increase in glutamate receptor functioning is associated with enhanced gene transcript levels of ionotropic NMDA and AMPA/kainate receptor subunits. These data reveal that morphine may progressively enhance glutamate neurotransmission within the nucleus accumbens core subsequent to drug exposure.