Tolerance to the eeg epileptiform change produced by enkephalin and cross-tolerance to morphine

EEG epileptiform patterns were produced by microinjections (0.5 ul, 10-20 ug) of leu-enkephalin into hippocampus, caudate nucleus and neocortex in cats and rats. Acute tolerance was demonstrated in all these structures after repeated administration at intervals ranging between 30 minutes to several hours. It consisted of the shortening and weakening of the EEG epileptiform effect when the same dose was given repeatedly and in the need for higher doses to repeat the initial effect. In most animals tolerance was observed at the second administration but in some it appeared only after several administrations. The duration of the tolerance period was correlated with the intensity of the initial effect. Morphine microinjections into hippocampus produced a similar EEG change which similarly showed tolerance. Tolerance produced to either enkephalin or morphine was transferred to the other drug.