The 5-HT3 receptor antagonists LY 277359 and granisetron potentiate the suppressant action of apomorphine on the basal firing rate of ventral tegmental dopamine cells.
In this study, we examined the effect of the 5-HT3 receptor antagonists LY 277359 and granisetron on the suppressant action of the dopamine receptor agonist (+/-)-apomorphine on spontaneously active dopamine cells in the substantia nigra pars compacta (SNC or A9) and ventral tegmentum area (VTA or A10) in the rat. This was accomplished using the standard extracellular single unit recording techniques. The i.v. administration of (+/-)-apomorphine (1-64 micrograms/kg) produced a dose-dependent suppression of the basal firing rate of spontaneously active A9 and A10 dopamine cells. The i.v. administration of LY 277359 at 0.01 and 0.1 mg/kg, but not 1 or 10 mg/kg, potentiated the suppressant action of (+/-)-apomorphine on A10 dopamine cell firing. In contrast, (+/-)-apomorphine's suppressant action on the firing rate of A10 dopamine neurons was potentiated by all doses of granisetron except the 10 mg/kg dose. The suppressant action of (+/-)-apomorphine in control and pretreated rats was reversed by the i.v. administration of haloperidol (0.05-0.1 mg/kg). In contrast, the suppression action of (+/-)-apomorphine on the firing rate of A9 dopamine cells was not altered by any dose of LY 277359 or granisetron. Overall, our results suggest that LY 277359 and granisetron selectively potentiate the response of A10 dopamine cells to (+/-)-apomorphine.
Minabe
Y
Y
Department of Psychiatry and Behavioral Sciences, State University of New York, Stony Brook 11794-8790.
Ashby
C R
CR
Schwartz
J E
JE
Wang
R Y
RY
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004298:Dopamine / Q000502:physiology*; D004357:Drug Synergism; D017829:Granisetron; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects
D001058:Apomorphine; D001572:Benzofurans; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004298:Dopamine; D017829:Granisetron; D007191:Indazoles; D012702:Serotonin Antagonists; C064877:zatosetron