5-HYDROXYINDOLE LEVELS IN RAT BRAIN AFTER INHIBITION OF DOPAMINE -HYDROXYLASE

¹ CNS Diseases Research, The Upjohn Company, Kalamazoo, Michigan

Endogenous brain norepinephrine (NE) levels were decreased within an hour after rats received U-14,624, 200 mg/kg; maximum depletion was detected after 12 hours. Brain 5-hydroxyindoleacetic acid (5-HIAA) concentrations were markedly increased concurrent with the inhibition of dopamine -hydroxylase and depletion of NE stores; maximum 5-HIAA was detected at 12 hours. Brain 5-hydroxytryptamine (5-HT) levels, after a short latency of two to three hours, also were increased during this same time interval. As enzyme inhibition was terminated and brain NE synthesis was initiated 12 to 18 hours after administration of inhibitor, brain 5-hydroxyindole levels fell gradually toward control levels. Brain 5-HIAA concentrations also were elevated coincident with decreased brain NE levels resulting from the administration of three other dopamine -hydroxylase inhibitors and also from the administration of U-14,624, 25 mg/kg. Disulfiram had little effect upon brain 5-HIAA. The initial linear rate of accumulation of brain 5-HIAA in probenecid-treated rats and of 5-HT in pargyline-treated rats was greater in animals which had been pretreated with U-14,624. The data support the conclusion that brain 5-HT synthesis was accelerated in rats with lowered brain NE. Possible mechanisms of NE and 5-HT interaction to explain these results are briefly discussed.

This article has been cited by other articles:

				J. C. Ballenger, F. K. Goodwin, L. F. Major, and G. L. Brown Alcohol and Central Serotonin Metabolism in Man Arch Gen Psychiatry, February 1, 1979; 36(2): 224 - 227. [Abstract] [PDF]