Analysis of the activation of dopamine metabolism by a serotonin uptake inhibitor.

The potentiation of the effect of haloperidol on rat striatal homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) by a serotonin (5-HT) uptake inhibitor, CGP 6085 A, has been further investigated. The evidence that this effect of CGP 6085 A is related to its 5-HT uptake inhibitory properties is discussed. The potentiation was antagonized by scopolamine and baclofen, and disappeared more rapidly than the uptake inhibitory effects of CGP 6085 A, presumably because the effects of uptake inhibition were counteracted by a reduction in 5-HT synthesis. CGP 6085 A also potentiated the effects of fluphenazine and pimozide, but not those of a number of other neuroleptics. It also failed to restore the effect of haloperidol in animals treated chronically with the neuroleptic. These results appear to indicate that CGP 6085 A can only stimulate DA neurons if their activity is already above the resting level. The antagonism of this effect by scopolamine suggests that the site of action of the 5-HT uptake inhibitor is before a cholinergic neuron.