[Antiepileptic action of met-enkephalin and the rapid development of tolerance to its epileptogenic action].

It has been shown in chronic experiments on rabbits with electrochemoelectrodes implanted into the dorsal hippocamp that the first administration of met-enkephalin in a dose of 60 to the hippocamp induced the development of an epileptogenic focus (EF) or potentiated the action of the penicillin-induced EF. The second administration of met-enkephalin in the same dose to the hippocamp (interval in a standard scheme of experiments 5 days) did not lead to the production of the EF, which attests to rapid development of tolerance to the epileptizing action of the peptide, with this tolerance being preserved for 20 subsequent days of observation over the animals. After tolerance developed, administration of 60 micrograms met-enkephalin 5 to 10 min before penicillin produced an antiepileptic action, thereby preventing the development of the EF. Met-enkephalin (0.1 and 1 microgram) did not epileptize hippocampal neurons but lowered the action of the penicillin-induced EF after the development of tolerance to the epileptizing action of a large dose of the peptide. The animals did not develop tolerance to the antiepileptic effect of met-enkephalin. The data obtained confirm the hypothesis that different opiate receptors are responsible for the epileptizing (delta-receptors) and antiepileptic (mu-receptors) action of the enkephalin. The effect of small doses of met-enkephalin appears to mirror to a greater degree the involvement of endogenous enkephalins in the epileptogenesis.