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Effects of bretylium and guanethidine on 3H-noradrenaline and 3H-serotonin release in rat brain cortex slices.

Rat brain cortex slices preincubated with 3H-noradrenaline or 3H-serotonin were superfused, and the effects of bretylium and guanethidine on the electrically evoked 3H overflow were studied. Bretylium inhibited the evoked tritium overflow both from slices labelled with 3H-noradrenaline and from those labelled with 3H-serotonin (by 49 and 74%, respectively, at 10(-4)M bretylium); the inhibitory effect on slices preincubated with 3H-serotonin was only slightly attenuated by paroxetine, an inhibitor of the neuronal serotonin uptake. Guanethidine inhibited (and at 10(-5)M even abolished) the evoked 3H overflow from slices labelled with 3H-noradrenaline, but it did not impair the tritium overflow from slices preloaded with 3H-serotonin. It is concluded that bretylium inhibits not only noradrenaline release, but also produces an even more pronounced inhibition of serotonin release. By contrast, guanethidine preferentially blocks noradrenergic neurones and hence, may be used as a pharmacological tool for studying the involvement of noradrenergic neurones in functions of the central nervous system.