The effects of d-amphetamine and potassium on serotonin release and metabolism in rat cerebral cortex tissue.

Chopped rat cerebral cortex tissue released tritiated serotonin (3H-5HT) when exposed to d-amphetamine (d-A) (10(-5)-10(-3)M) or potassium ion (K) (24-60mM). The d-A-induced release was not dependent upon calcium, whereas, K-induced release was dependent upon calcium. Potassium caused a significant increase in the percentage of 3H-5-hydroxyindoleacetic acid (3H-5HIAA) released from the tissue. The increased metabolite was formed totally by oxidative deamination as shown by inhibition of the formation and release of 3H-5HIAA following inhibition of monoamine oxidase with clorgyline. The increased deamination as a result of incubation with K apparently occurred prior to release of 5HT from the nerve terminal, since incubation of the tissue with fluoxetine, a selective 5HT uptake inhibitor, did not alter the increased 3H-5IAA formation in response to K. These findings indicate that d-A and K apparently release 3H-5HT by different mechanisms and emphasize the importance of measuring metabolite formation in studies examining the effects of drugs on the release of 5HT in vitro.