The effects of antidepressants on the retention and metabolism of [3H]-norepinephrine in rat brain slices

Abstract

Tricylic antidepressants acutely decrease the neuronal retention of [3H]-norepinehrine ([3H]-NE) by blocking neuronal membrane uptake and/or vesicular uptake and binding. To distinguish between effects upon the plasma membrane and upon the vesicular membrane, the retention, deamination, and O-methylation of [3H]-NE by rat brain slices were investigated in the presence of several antidepressant agents. The effects of antidepressants were compared to those of the prototype inhibitors, cocaine and reserpine, using slices of hypothalamus, brainstem. parietal cortex and caudate nucleus. Cocaine, which inhibits neuronal membrane uptake, decreased both the deamination and retention of [3H]-NE, while O-methylation was increased. Reserpine, which inhibits vesicular transport and binding, increased deamination, while it reduced retention without affecting the 0-methylation of [3H]-NE. The effects of desipramine, a prototype tricyclic antidepressant, were found to depend on the concentration. At low concentrations (10-9-10-8M), desipramine inhibited the retention and deamination of [3H]-NE in each brain region except the caudate. At higher concentrations (10-7-10w-4M), the retention of [3H]-NE was reduced further. However, deamination was increased in the caudate and, in the other three regions, deamination did not decrease further. Nortriptyline and protriptyline had actions similar to desipramine, whereas, iprindole did not affect [3H]-NE retention. These results suggest that tricyclic antidepressants are not specific selective inhibitors of neuronal membrane transport.