Increased dopamine and serotonin metabolites in CSF during severe insulin-induced hypoglycemia in freely moving rats

The effect of insulin on dopamine (DA) and serotonin (5-HT) metabolites was determined in the cerebrospinal fluid (CSF) of the rat and compared with glucose levels in blood and CSF. CSF was continuously withdrawn from the third ventricle of freely moving rats at a constant rate of 1 μl/min. Liquid chromatography with electrochemical detection was used for the direct assay of DA and 5-HT metabolites in the CSF. The metabolites were stable during the first hour after insulin injection (6IU/Kg). A progressive increase occurred thereafter in animals which had no access to food during the time of the experiment. The maximal effect was observed 2.5 h after insulin, with respective mean increases of 80% for dihydroxyphenylacetic acid, 47% for homovanillic acid and 33% for 5-hydroxyindolacetic acid. These increases in monoamine metabolites were not observed when rats received glucose (5g/Kg ip) 45 min after insulin or when food was made available. The period for insulin-induced increase in DA and 5-HT metabolites corresponded to a maximal fall of glucose levels both in blood and CSF although the CSF glucose decrease was delayed when compared to the fall of blood glucose. The role of brain glucose and brain insulin in the control of central DA and 5-HT metabolism is discussed.