An alternate role of GIRK channels in opioid dependence is suggested by the following observations. Mice lacking GIRK2 and GIRK3 have strongly reduced withdrawal signs normally induced in wild-type controls by the opioid receptor antagonist naloxone after chronic exposure to morphine. In the mutant mice, the withdrawal syndrome can be rescued if the output from locus coeruleus neurons is inhibited during the exposure to morphine30. This suggests that GIRK channels ‘gate’ the induction of opioid dependence by silencing the neurons in the locus coeruleus every time opioids are injected.
