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.
Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
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E
Carboni
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E
Acquas
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R
Frau
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Di Chiara
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