INTERACTIONS OF FLUOXETINE WITH METABOLISM OF DOPAMINE AND SEROTONIN IN RAT-BRAIN REGIONS

Given evidence of inhibitory effects of serotonin on dopaminergic neurotransmission. a series of experiments sought neurochemical evidence of interactions between the selective serotonin transport inhibitor fluoxetine and the metabolism of dopamine (DA) or serotonin (5-HT) in regions of rat brain that might account for extrapyramidal side-effects associated with clinical use of fluoxetine. There were significant inhibitory effects of acute or repeated fluoxetine treatment on the turnover of 5-HT (accumulation of 5-hydroxytryptophan, or ratio of [5-hydroxyindoleacetic acid]/[5-HT]) in striatum, nucleus accumbens and frontal cerebral cortex, but only minor effects on metabolism of DA (accumulation of dihydroxyphenylalanine, or [homovanillic acid]/[DA] ratio), even at high doses or with repeated treatment, and no significant inhibition of the DA metabolism-increasing actions of haloperidol.