Using the drug discrimination paradigm, we aimed to compare the detection of internal opioid signals in GluA1−/− and GluA1+/+ mice. In discrimination training, both genotypes equally learned to discriminate morphine during the 40 training sessions (genotype effect, F1,12 = 0.15, p>0.05). Females reached the training criteria in fewer sessions than males (sessions to reach criteria were 61 and 35 for males and females, respectively; sex effect, F1,12 = 6.45, p<0.05). However, no genotype×sex interaction was found (F1,12 = 1.25, p>0.05). Of a total of 21 animals, 5 failed to reach the training criteria for reliable morphine discrimination in 40 training session (three female GluA1+/+ mice and one male and one female GluA1−/− mouse) and were therefore excluded from the analyses.