Electrophysiological signs of differential tolerance development to morphine in selected areas of the rabbit brain

Electrical activity in discrete populations of neurons (multiple-unit activity) was monitored simultaneously in six brain regions of New Zealand rabbits chronically treated with morphine. Morphine sulfate was administered b.i.d. at 10, 20, and 30 mg/kg/ injection, for three days at each dose. Multiple-unit activity was recorded intermttently for ten hours after the morning injection each day. The effect of morphine on all brain areas of naive rabbits was depression of multiple-unit activity; the caudate, dorsal hippocampus, and accumbens were most depressed. With succeeding days the drug-induced depression became less marked, and this is interpreted as evidence for tolerance development. Conspicuosly less evidence for tolerance was noted in periaqueductal grey matter. In some regions, subsequent morphine injections increased multiple-unit activity over control values; this effect was most pronounced in the medial thalamus and mesencephalic reticular formation. These data may be interpreted as evidence for different brain regions being involved with different aspects of opiate action.