Selective reduction of extracellular dopamine in the rat nucleus accumbens following chronic treatment with DAU 6215, a 5-HT3 receptor antagonist

R. Invernizzi, L. Pozzi, R. Samanin

Research output: Contribution to journalArticle

Abstract

The effect of chronic treatment with (3-α-tropanyl)1H-benzimidazolone-3-carboxamide chloride (DAU 6215; 15 μg/kg s.c. twice daily for 21 days), a Serotonin3 receptor antagonist, on the extracellular concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was studied by intracerebral dialysis in the striatum, nucleus accumbens and frontal cortex of conscious rats. Twenty-four hours after the last injection, the basal extracellular concentrations of DA in the nucleus accumbens of rats given DAU 6215 were significantly lower than in saline-treated rats. DA output in the dorsolateral striatum or frontal cortex was not significantly different between the DAU 6215 and saline-treated rats.Chronic DAU 6215 significantly reduced the extracellular concentrations of DOP AC and HVA in the frontal cortex but had no effect in the other brain regions. A subcutaneous challenge dose of DAU 6215 (15 μg/kg) did not significantly modify the extracellular concentrations of DA and its metabolites in either DAU 6215 or saline treated rats in any of the brain regions examined. The present investigation is the first on the effect of chronic administration of a 5-HT3 receptor antagonist on basal extracellular DA in the rat brain. The results provide evidence of an association between the electrophysiological and biochemical effects of chronic treatment with a serotonin3 receptor antagonist on the activity of the mesolimbic DA system. In line with the theory that hyperactivity of the mesolimbic dopaminergic system is involved in psychosis, the results suggest that DAU 6215 may be useful in the treatment of psychotic disorders, possibly with limited extrapyramidal effects.

Original languageEnglish
Pages (from-to)211-215
Number of pages5
JournalNeuropharmacology
Volume34
Issue number2
DOIs
Publication statusPublished - 1995

Keywords

  • 5-HT receptor
  • chronic treatment
  • Dopamine release
  • dorsolateral striatum
  • frontal cortex
  • microdialysis
  • nucleus accumbens

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology
  • Drug Discovery

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