The effect of acute and chronic LY 277359, a selective 5-HT3 receptor antagonist, on the number of spontaneously active midbrain dopamine neurons.
In this study, we have examined the effect of acute and chronic administration of LY 277359, a putative 5-HT3 receptor antagonist, on the number of spontaneously active dopamine cells in the substantia nigra pars compacta (SNC or A9) and ventral tegmental area (VTA or A10). This was accomplished using the standard extracellular single unit recording techniques. The acute administration of LY 277359 (0.1 or 1.0 mg/kg i.p.) produced a significant increase in the number of spontaneously active A10, but not A9, dopamine cells compared to saline controls. The acute administration of 10 mg/kg of LY 277359 did not significantly alter the number of spontaneously active dopamine cells in either area. In contrast to its acute effects, the administration of 0.1 mg/kg per day of LY 277359 for 21 days decreased the number of spontaneously active A9 and A10 dopamine cells. However, the i.v. administration of (+/-)-apomorphine (50 micrograms/kg) did not reverse LY 277359's action, suggesting that the chronic LY 277359-induced reduction of dopamine cells was not the result of depolarization block. To test whether chronic administration of LY 277359 at a high dose would induce depolarization block of dopamine cells, rats were treated with 1.0 or 10 mg/kg LY 277359. Interestingly, the chronic administration of 1.0 mg/kg LY 277359 increased the number of A10, but not A9 dopamine cells. In contrast, chronic treatment with 10 mg/kg selectively decreased the number of spontaneously active A10 dopamine cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Minabe
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Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794-8790.
Ashby
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Wang
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D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004298:Dopamine / Q000502:physiology*; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects
D001572:Benzofurans; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; C064877:zatosetron; D004298:Dopamine