EFFECTS OF KETAMINE ON DOPAMINE METABOLISM DURING ANESTHESIA IN DISCRETE BRAIN-REGIONS IN MICE - COMPARISON WITH THE EFFECTS DURING THE RECOVERY AND SUBANESTHETIC PHASES

The effects of ketamine on the levels of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT, serotonin) and their metabolites wer e examined in discrete brain regions in mice. A high dose of ketamine (150 mg/kg, i.p.) did not change DA metabolism in the frontal cortex, nucleus accumbens, striatum and hippocampus, but did decrease it in th e brainstem during anesthesia. In contrast, during recovery from the k etamine anesthesia, the high dose increased the level of homovanillic acid (HVA) in all brain regions. A low subanesthetic dose of ketamine (30 mg/kg, i.p.) increased the concentrations of both 3,4-dihydroxyphe nylacetic acid (DOPAC) and HVA only in the nucleus accumbens. The DA l evel was not affected by any ketamine treatment. During ketamine anest hesia, the content of 3-methoxy-4-hydroxy-phenylglycol (MHPG) was decr eased in the brainstem, whereas during recovery from anesthesia, the M HPG level was increased in the frontal cortex, nucleus accumbens and b rainstem. The NE content was not altered in any region by ketamine tre atment. The concentration of 5-hydroxyindoleacetic acid (5-HIAA) was r educed in the frontal cortex, striatum, hippocampus and brainstem duri ng ketamine anesthesia. The 5-HT level was unaltered in all regions ex cept the brainstem where it was reduced. In contrast, after anesthesia , the concentrations of both 5-HT and 5-HIAA were increased in the str iatum. During the subanesthetic phase, however, the levels of NE, 5-HT and their metabolites were unchanged. These neurochemical results are consistent with the electrophysiological findings that a high dose of ketamine does not change the basal firing rates of nigrostriatal DA n eurons during anesthesia, while low subanesthetic doses significantly increase those of ventral tegmental DA neurons. (C) 1997 Elsevier Scie nce B.V.