MOR KI mice contain the amino acid mutation T394A in exon 4 of the opioid receptor, mu 1 (Oprm1) gene. These receptors are expressed throughout the neocortex, thalamus, nucleus accumbens, hippocampus, and amygdala, as well as in the peripheral nervous system, and have been associated with pain sensitivity. The MOR also has an important role in dependence to drugs of abuse, such as opioid, nicotine, cocaine, and alcohol via its modulation of the dopamine system. Binding of these drugs increases the release of beta-endorphins, which subsequently increase release of dopamine and stimulates cravings. T394 of the MOR is a crucial residue for initiation of agonist-induced opioid receptor phosphorylation. Homozygotes are viable and fertile. This mutation alters opioid tolerance and vulnerability to opioid abuse and dependence. Mice exhibit attenuated opioid tolerance, enhanced vulnerability to heroin self-administration, enhanced brain dopamine response to heroin, and enhanced opioid withdrawal.
