Serotonin--dopamine Interactions in the Nigrostriatal System

A study was made of the effects of serotonin uptake inhibition and receptor blockade on the increase in rat striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid and on some behavioural responses induced by haloperidol. The serotonin uptake inhibitors CGP 6085 A (4-(5,6-dimethyl-2-benzofuranyl)-piperidine-HCl), citalopram (Lu 10-171), fluoxetine (Lilly 110140), and clomipramine potentiated the increase in striatal deaminated dopamine metabolites after the neuroleptic. In contrast, the serotonin antagonists methysergide, mianserin and cinanserin antagonized the acceleration of dopamine turnover induced by haloperidol. The catalepsy induced by this neuroleptic was potentiated by CGP 6085 A and citalopram. These 5-HT uptake inhibitors also potentiated the antagonism by haloperidol of apomorphine-induced stereotypies. These results seem to make it worthwhile to test a combination of haloperidol and a serotonin antagonist in schizophrenic patients to see whether the ratio of the therapeutic effect to the extrapyramidal side effects can be improved.