Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release.
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.
Carboni
E
E
Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
Acquas
E
E
Frau
R
R
Di Chiara
G
G
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000077526:Tropisetron
D007211:Indoles; D012702:Serotonin Antagonists; D000431:Ethanol; D000077526:Tropisetron; D009538:Nicotine; D009020:Morphine; D000661:Amphetamine; D006220:Haloperidol; D004298:Dopamine