The 5-HT3 receptor antagonist zatosetron decreases the number of spontaneously active A10 dopamine neurons.
Acute and chronic administration of low doses (e.g. 0.1, 0.3 mg/kg i.p.) of the selective 5-HT3 antagonist zatosetron decreased the number of spontaneously active A 10 dopamine cells but did not change the number of spontaneously active A9 dopamine cells; higher doses (1.0, 10 mg/kg) were less effective. The decrease in the number of spontaneously active A 10 dopamine cells following zatosetron administration was not reversed by the administration of apomorphine. These data indicate that zatosetron's effects on spontaneously active dopamine neurons: (1) differs from other 5-HT3 antagonists; (2) may not be mediated by depolarization inactivation; and, (3) may be predictive of an atypical antipsychotic action without delayed onset.
Rasmussen
K
K
Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285.
Stockton
M E
ME
Czachura
J F
JF
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002452:Cell Count / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D001572:Benzofurans; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; C064877:zatosetron; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine