Ketamine inhibits serotonin synthesis and metabolism in vivo.
Ketamine (160 mg/kg, i.p.) was found to reduce the accumulation of 5-hydroxytryptophan (5-HTP) in whole brain following inhibition of L-aromatic amino acid decarboxylase with 50 mg/kg of 3-hydroxybenzylhydrazine (NSD-1015). Smaller doses of ketamine did not affect whole brain 5-HTP accumulation. However in regional studies, 80 mg/kg of ketamine significantly reduced 5-HTP accumulation in the spinal cord and the midbrain-thalamus. A dose of 160 mg/kg ketamine also reduced 5-HTP accumulation in the spinal cord and midbrain-thalamus and in the medulla-pons, striatum and cortex as well. No significant changes in 5-HTP accumulation were observed in the hypothalamus or hippocampus. Ketamine (160 mg/kg) also reduced whole brain 5-hydroxyindoleacetic acid (5-HIAA) levels and slightly elevated whole brain 5-hydroxytryptamine (5-HT) levels. Smaller doses did not affect either 5-HIAA or 5-HT levels. Ketamine did not affect whole brain tryptophan levels nor did it inhibit [3H]tryptophan uptake or conversion to [3H]5-HT in vitro. These data demonstrate that ketamine reduced both 5-HT synthesis and metabolism in vivo. Since ketamine did not affect brain tryptophan levels nor did it inhibit 5-HT in vitro, the reduction of 5-HT turnover following ketamine administration appears to be a neuronal, adaptive phenomenon possibly occurring in response to a blockade of 5-HT uptake by ketamine.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003864:Depression, Chemical; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D007649:Ketamine; D014364:Tryptophan