Detection of opioid stimulus was found to be intact in GluA1−/− mice, since these mice were able to discriminate between the levers associated with morphine and saline when different doses of morphine were administered at the drug discrimination test. The GluA1−/− mice learned the food-reinforced lever-pressing similarly to their wildtype controls, thus providing a stable platform to study drug discrimination and confirming the previous data that GluA1 subunit is not critical in learning the simple food-reinforced lever-pressing task [14]. Unchanged perception of morphine effects by these mice was indicated by the unchanged dose-response of morphine-appropriate responding. To our knowledge, these are the first morphine discrimination studies reported for mice. Importantly, most opioid-related mechanisms and processes that have been studied, have been unaltered in the GluA1−/− mice. They have unaltered pharmacodynamics evidenced by unchanged μ-opioid receptor signaling at the G-protein level in various brain regions (the present study), morphine-induced sensitization and morphine-induced analgesia [16] and pharmacokinetics evidenced by unchanged morphine concentrations in blood and brain tissue after acute administration [16]. Thus, the target systems for morphine appear to be normally functional in the GluA1−/− mice.
