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- W1982063323 abstract "Baclofen, by inhibiting DA neurons, increases intraneuronal DA and its deaminated metabolites in the striatum, due to decreased DA utilisation followed only later by reduced synthesis. B similarly affects striatal 5-HT. This is prevented by lesion of the nigrostriatal DA system, indicating that the latter mediates the effects of B on striatal 5-HT. After repeated administration of 30 mg/kg IP B, its effects on DA and its metabolites as well as that on 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) are reduced. The time-course of the development of this “tolerance” is similar for the DA (t12 of regression of DA levels = 3.1 days) and 5-HT (t12 = 3.0 days) system. This supports the previous suggestion that B effects on 5-HT are mediated by the DA system and indicates that the “tolerance” developed by the latter has functional consequences. Incidentally, tolerance to 1 mg/kg PO haloperidol (acutely maximally increasing homovanillic acid levels) develops with a t12 of 2.8 days. This may indicate a common basic adaptional mechanism. Some 5-HT agonists and antagonists alter the effect of B on striatal 5-HT metabolism. Metergoline (0.125-1 mg/kg IP) increases the effect of B on 5-HIAA and, less, on 5-HT. Methysergide (2–20 mg/kg IP), quipazine (0.625-5 mg/kg IP) and the 5-HT uptake blocker CGP 6085 (0.3–10 mg/kg PO) decrease the effect of B on 5-HIAA); only CGP 6085 reduces 5-HIAA levels on its own. Mianserin (5–20 mg/kg IP) does not alter B effects. Differential actions of these drugs on pre- and postsynaptic 5-HT receptors could be responsible for these results." @default.
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- W1982063323 date "1980-01-01" @default.
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- W1982063323 title "Effects of baclofen on striatal dopamine and serotonin metabolism" @default.
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