Chronic diazepam treatment in rats causes long-lasting changes in central [3H]-5-hydroxytryptamine and [14C]-gamma-aminobutyric acid release

P K Hitchcott, S E File, M Ekwuru, M J Neal

Research output: Contribution to JournalArticlepeer-review

Abstract

The effects of chronic diazepam administration to rats on the central release of [3H]-5-hydroxytryptamine ([3H]-5-HT) and [14C]-gamma-aminobutyric acid ([14C]-GABA, ex vivo) were examined. Chronic (5 and 21 days) administration of diazepam (4 mg kg-1 i.p. daily for 21 days) reduced the K-evoked (20 mM KCl) release of [3H]-5-HT from frontal cortex by approximately 50%. Remarkably, this decrease was still present 1 week after diazepam withdrawal. Chronic diazepam treatment did not significantly affect hippocampal [3H]-5-HT release but after 21 days the K-evoked release of [14C]-GABA was more than doubled and remained elevated 30 h after withdrawal; it returned to control levels after 1 week, and decreased below control levels after 2 weeks. This study indicates that chronic diazepam treatment produces striking changes in transmitter release in rats that persist long after treatment has ceased.

Original languageEnglish
Pages (from-to)11-12
Number of pages2
JournalBritish Journal of Pharmacology
Volume99
Issue number1
DOIs
Publication statusPublished - Jan 1990

Keywords

  • Animals
  • Brain Chemistry/drug effects
  • Cerebral Cortex/drug effects
  • Diazepam/pharmacology
  • Hippocampus/drug effects
  • Male
  • Rats
  • Serotonin/metabolism
  • Substance Withdrawal Syndrome/metabolism
  • gamma-Aminobutyric Acid/metabolism

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