Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release

Eur J Pharmacol. 1989 May 30;164(3):515-9. doi: 10.1016/0014-2999(89)90259-8.

Abstract

The effects of a potent and specific antagonist of 5-HT3 receptors, ICS 205-930, on the dopamine (DA)-releasing properties of morphine (1.0 mg/kg s.c.), nicotine (0.6 mg/kg s.c.), ethanol (1.0 g/kg i.p.) and amphetamine (0.25 and 1.0 mg/kg s.c.) were studied in rats. DA release was estimated by trans-cerebral dialysis in the nucleus accumbens of freely moving rats. ICS 205-930 (15-30 micrograms/kg s.c.) failed to modify the basal output of DA and its metabolites, however, ICS 205-930 dose dependently reduced the stimulation of DA release by morphine, nicotine and ethanol. Thus, at doses of 30 micrograms/kg s.c., ICS 205-930 completely prevented the morphine-, nicotine- and ethanol-induced stimulation of DA release in the nucleus accumbens; doses of 15 micrograms/kg s.c. partially prevented the morphine-, nicotine- and ethanol-induced stimulation of DA release while doses of 7.5 micrograms/kg s.c. were ineffective. In contrast, ICS 205-930 (up to 30 micrograms/kg s.c.) failed to affect the amphetamine-induced stimulation of DA release in the nucleus accumbens. The inhibitory effects of ICS 205-930 (15 and 30 micrograms/kg s.c.) on the drug-induced stimulation of DA release could also be extended to the neuroleptic haloperidol (0.1 mg/kg s.c.). The results indicate that blockade of 5-HT3 receptors selectively prevents the stimulation of DA release induced by drugs known to stimulate the firing activity of DA neurons.

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Brain Chemistry / drug effects
  • Dialysis
  • Dopamine / metabolism*
  • Ethanol / pharmacology
  • Haloperidol / pharmacology
  • Indoles / pharmacology
  • Male
  • Morphine / pharmacology
  • Nicotine / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Serotonin Antagonists / pharmacology*
  • Tropisetron

Substances

  • Indoles
  • Serotonin Antagonists
  • Ethanol
  • Tropisetron
  • Nicotine
  • Morphine
  • Amphetamine
  • Haloperidol
  • Dopamine