MOPr desensitization in mature LC neurons is not at the level of the GIRK channel. (A) In the continued presence of the GIRK blocker rTertiapinQ (100 nm), outward potassium current was recorded from a single LC neuron in a brain slice from a mature rat in response to application of a submaximal concentration of noradrenaline (NA; 5 μm) or a maximally effective concentration of DAMGO (10 μm), reversed with the MOPr antagonist naloxone (Nal; 5 μm). The response to DAMGO desensitized in the continued presence of the drug, whereas the response to NA which was applied both before and after the DAMGO treatment was unchanged. Pooled data from experiments as in A show that (B) the mean peak amplitudes of DAMGO-elicited potassium currents were significantly inhibited by the presence of rTertiapinQ (*P < 0.05 vs. control, Student's t-test; n = 5–7) and that (C) whereas the DAMGO response rapidly desensitized [**P < 0.001, one-sample Student's t-test (t6 = 26.08, P < 0.0001), n = 7], there was no significant decline in the NA response after DAMGO-induced MOPr desensitization (P > 0.05, n = 7).