Tolerance to opioids in single locus coeruleus neurons of the rat

Chronic treatment of rats with morphine caused tolerance to the membrane hyperpolarizing action of morphine in single locus coeruleus neurons in vitro. Tolerance was less pronounced for Try-D-Ala-Gly-MePhe-Gly-ol (DAGO) than for normorphine. No changes were found in affinity of naloxone for mu-receptors on these neurons, nor in the properties of the potassium conductance increase caused by mu-receptor activation. These results suggest that the mechanisms underlying tolerance involve either a reduction of the number of mu-receptors on each cell, or a reduced coupling of mu-receptors to potassium channels.