Anticonvulsant and proconvulsant actions of alpha- and beta-noradrenergic agonists on epileptiform activity in rat hippocampus in vitro.

Abstract

The ability of l-norepinephrine to influence epileptiform activity was examined in an in vitro rat hippocampal slice preparation. Exogenously applied norepinephrine (NE) had anticonvulsant properties in that it slowed or stopped spontaneous interictal discharges which had been initiated by superfusion of slices with medium containing penicillin and elevated levels of potassium. This anticonvulsant property of NE was shared by the alpha receptor agonists 6-fluoro-norepinephrine, l-alpha-methyl-norepinephrine, and clonidine, but not by d-alpha-methyl-norepinephrine or l-phenylephrine. The beta receptor agonists 2-fluoro-norepinephrine and l-isoproterenol, on the other hand, were proconvulsant in that they increased interictal discharge rate. The alpha receptor antagonist phentolamine selectively blocked anticonvulsant responses, whereas the beta receptor antagonist timolol selectively blocked proconvulsant activity. These results suggest that activation of alpha or beta receptors has opposing inhibitory or excitatory effects respectively on epileptiform discharges in the rat hippocampus.