Acute or chronic changes of noradrenergic transmission do not affect the α-adrenoceptor-mediated inhibition of ³H-serotonin release in the cerebral cortex

Summary

Rat brain cortex slices preloaded with either ³H-serotonin or ³H-noradrenaline were superfused with physiological salt solution, and tritium overflow was evoked by electrical field stimulation.

• 1. After exposure to guanethidine plus paroxetine (an inhibitor of serotonin uptake) during a 15-min incubation period prior to superfusion, the evoked overflow from slices labelled with ³H-noradrenaline was strongly inhibited, where-as that from slices labelled with ³H-serotonin remained virtually unaffected. In the absence of paroxetine, exposure to guanethidine inhibited the evoked overflow both from slices labelled with ³H-noradrenaline and those labelled with ³H-serotonin.

• 2. Noradrenaline inhibited the evoked overflow from slices preloaded with ³H-serotonin in a concentration-dependent manner. This effect was not substantially affected by exposure to guanethidine plus paroxetine before superfusion.

• 3. Intracerebroventricular injection of 6-hydroxydopamine (6-OH-DA) or long-term pretreatment of rats with desipramine did not significantly alter the inhibitory effect of noradrenaline on evoked overflow from slices preincubated with ³H-serotonin.

• 4. The percentage of ³H-serotonin contained in evoked tritium overflow was neither altered by pretreatment of rats with 6-OH-DA or desipramine nor by exposure of the slices to guanethidine or noradrenaline.

It is concluded that guanethidine inhibits not only noradrenaline but also serotonin release from the corresponding neurones of the cerebral cortex and that the selectivity for serotonin uptake. Acute or chronic impairment of noradrenaline release by guanethidine and 6-OH-DA, respectively, or long-term inhibition of noradrenaline uptake by desipramine does not affect the α-adrenoceptor-mediated inhibition of serotonin release.