The role of 5-HT(2A) receptor antagonism in amphetamine-induced inhibition of A10 dopamine neurons in vitro.
The role of the 5-HT(2A) receptor in modulating amphetamine-induced inhibition of dopamine neuronal firing in A9 and A10 was investigated in rat midbrain slices. The antipsychotic drugs olanzapine and clozapine more potently reversed the amphetamine-induced inhibition in A10 neurons compared to A9 neurons. Risperidone (0.03 and 0.1 microM) reversed amphetamine-induced inhibition of firing activity similarly in A9 and A10. The dopamine D2 receptor antagonist (-)sulpiride (0.05 and 1 microM) reversed the amphetamine (10 microM)-induced inhibition of firing activity in A9 and A10 neurons. The selective 5-HT(2A) receptor antagonist MDL 100907 (0.05 microM), strongly enhanced the reversal of amphetamine-induced inhibition by (-)sulpiride in A10, but its effectiveness was much smaller in A9 dopamine neurons. We conclude that 5-HT(2A) receptor antagonism enhanced reversal of amphetamine-induced inhibition by dopamine D2 antagonism in A10, suggesting that dopamine D(2) receptor antagonism combined with 5-HT(2A) receptor antagonism may play a role in antipsychotic drug atypicality.
Olijslagers
Johanna E
JE
Swammerdam Institute for Life Sciences, Center for NeuroScience, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands. olijslag@science.uva.nl
Perlstein
Benny
B
Werkman
Taco R
TR
McCreary
Andrew C
AC
Siarey
Richard
R
Kruse
Chris G
CG
Wadman
Wytse J
WJ
D000200:Action Potentials / Q000187:drug effects; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D000077152:Olanzapine; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000502:physiology; D058830:Serotonin 5-HT2 Receptor Antagonists; D013469:Sulpiride / Q000494:pharmacology
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D005464:Fluorobenzenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D058830:Serotonin 5-HT2 Receptor Antagonists; D001569:Benzodiazepines; D013469:Sulpiride; D000661:Amphetamine; C079049:volinanserin; D003024:Clozapine; D000077152:Olanzapine; D004298:Dopamine