Alterations in brain 5-hydroxytryptamine metabolism during the 'withdrawal' phase after chronic treatment with diazepam and bromazepam.
1 Daily administration of diazepam or bromazepam (10 mg/kg) for 22 days significantly increased the activity of mid-brain tryptophan hydroxylase by 36% and 39%, respectively. The concentration of tryptophan was also enhanced in the mid-brain region of rats subjected to benzodiazepine treatment.2 Chronic therapy with either of the two anti-anxiety agents enhanced the endogenous levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cerebral cortex, hypothalamus, pons-medulla, mid-brain and striatum.3 Whereas diazepam treatment decreased (13%) the activity of monoamine oxidase in mid-brain, bromazepam failed to exert any effect, suggesting that the observed elevation in 5-hydroxy-indoleacetic acid levels is not associated with enhanced deamination of 5-hydroxytryptamine.4 Discontinuation of treatment for 48 h significantly decreased the activity of mid-brain tryptophan hydroxylase to levels that were significantly lower than those seen for benzodiazepine-treated and normal rats. The concentrations of mid-brain tryptophan and 5-hydroxytryptamine were also reduced in various brain regions examined.5 Withdrawal from diazepam or bromazepam therapy further augmented the levels of brain 5-hydroxyindoleacetic acid.6 The results demonstrate that the depressant effects on behaviour of these agents are accompanied by increased metabolism of 5-hydroxytryptamine in the brain. Withdrawal from these minor tranquillizers, on the other hand, reduces the synthesis of this indoleamine.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D001960:Bromazepam / Q000008:administration & dosage / Q000494:pharmacology*; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000201:enzymology / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D014151:Anti-Anxiety Agents; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase; D003975:Diazepam; D001960:Bromazepam