Deletion of the glutamate receptor 5 subunit of kainate receptors affects the development of morphine tolerance.

Previous reports utilizing pharmacological antagonists implicate kainate receptor (KAR) activation in the development of morphine tolerance, dependence, conditioned place preference (CPP), and locomotor sensitization, but the role of glutamate receptor (GluR) 5-containing KAR in these effects remains unclear because of limited selectivity of the inhibitors employed. Therefore, we examined responses to systemic morphine treatment in mice expressing a constitutive deletion of GluR5 [GluR5 knockout (KO)]. Unlike wild-type (WT) littermates, GluR5 KO mice do not develop tolerance after repeated morphine administration by subcutaneous injection or via subcutaneous pellet implantation.

A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain.

To determine the importance of the NMDA receptor (NMDAR) in pain hypersensitivity after injury, the NMDAR1 (NR1) subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection, and NMDA currents, but not AMPA currents, are reduced 86-88% in lamina II neurons. The spatial NR1 knock-out does not alter heat or cold paw-withdrawal latencies, mechanical threshold, or motor function.