Chronic treatment with DAU 6215, a new 5-HT3 receptor antagonist, causes a selective decrease in the number of spontaneously active dopaminergic neurons in the rat ventral tegmental area

Simona Prisco, Mauro Pessia, Angelo Ceci, Franco Borsini, Ennio Esposito

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Electrophysiological techniques were used to study the effects of the new compound, DAU 6215 ((3-α-tropanyl) 1H-benzimidazolone-3-carboxamide chloride), a selective 5-HT3 receptor antagonist, on the activity of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Acute i.v. injections of DAU 6215 did not cause any change in the basal firing rate of DA neurons in the SNc or in the VTA. Pretreatment with DAU 6215 did not modify the inhibitory effect of apomorphine on the firing rate of midbrain DA neurons. Acute s.c. administration of DAU 6215 caused a significant increase in the number of spontaneously active DA neurons in the VTA but not in the SNc. This effect was similar to that of acute clozapine, whereas acute haloperidol caused a significant increase of spontaneously active DA neurons in both the SNc and the VTA. Repeated consecutive s.c. administration of DAU 6215 and clozapine for 21 days produced a significant decrease in the number of spontaneously active DA neurons in the VTA but not in the SNc. Chronic haloperidol (21 days) decreased the number of DA cells both in the SNc and VTA. The effect of chronic DAU 6215 on the activity of VTA DA neurons was reversed by apomorphine, suggesting that these neurons were probably under a state of depolarization block. These findings indicate that DAU 6215 may have potential antipsychotic activity, probably associated with a low incidence of extrapyramidal side-effects.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalEuropean Journal of Pharmacology
Volume214
Issue number1
DOIs
Publication statusPublished - Apr 7 1992
Externally publishedYes

Keywords

  • 5-HT receptors
  • Antipsychotic drugs
  • DAU 6215
  • Depolarization block
  • Dopamine neurons

ASJC Scopus subject areas

  • Pharmacology

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