Alterations in brain 5-hydroxytryptamine metabolism during the 'withdrawal' phase after chronic treatment with diazepam and bromazepam

Br J Pharmacol. 1977 May;60(1):3-9. doi: 10.1111/j.1476-5381.1977.tb16740.x.

Abstract

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.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Brain / metabolism*
  • Bromazepam / administration & dosage
  • Bromazepam / pharmacology*
  • Diazepam / administration & dosage
  • Diazepam / pharmacology*
  • Humans
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Mesencephalon / enzymology
  • Mesencephalon / metabolism
  • Monoamine Oxidase / metabolism
  • Rats
  • Serotonin / metabolism*
  • Substance Withdrawal Syndrome / metabolism*
  • Time Factors
  • Tryptophan / metabolism
  • Tryptophan Hydroxylase / metabolism

Substances

  • Anti-Anxiety Agents
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Tryptophan
  • Tryptophan Hydroxylase
  • Monoamine Oxidase
  • Diazepam
  • Bromazepam