Inhibition by aripiprazole of dopaminergic inputs to striatal neurons from substantia nigra.
BACKGROUND
Aripiprazole (OPC-14597) elicits both dopamine D(2) agonist and antagonist activities on dopaminergic neurons of the ventral tegmental area and nucleus accumbens neurons, respectively. However, the electrophysiological action of this drug on the striatal neurons is not clear.


OBJECTIVE
Therefore, the present electrophysiological study was performed to determine if aripiprazole modified the striatal neurons as a D(2) receptor agonist or antagonist.


METHODS
Spikes elicited by stimulation of pars compacta of the substantia nigra (SN) were extracellularly recorded from the striatal neurons with a glass microelectrode attached along a seven- barreled micropipette. Each barrel was filled with aripiprazole, quinpirole (D(2) receptor agonist), domperidone (D(2) receptor antagonist), glutamate or 2 M NaCl. The drugs were microiontophoretically applied on the neurons being recorded.


RESULTS
The effects of aripiprazole on SN stimulation-induced spikes of striatal neurons that were inhibited by domperidone were examined. Microiontophoretic application of aripiprazole inhibited spikes elicited by SN stimulation in all 18 neurons tested in a dose-dependent manner. In addition, quinpirole-induced firing was inhibited by aripiprazole in all ten neurons tested. However, glutamate-induced spontaneous firing was not affected by aripiprazole in any of the ten neurons tested.


CONCLUSIONS
These findings suggest that aripiprazole acts as a dopamine D(2) receptor antagonist on striatal neurons receiving excitatory inputs from the SN.
Matsubayashi
H
H
Department of Pharmacology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Amano
T
T
Sasa
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010879:Piperazines; D015363:Quinolones; D004294:Domperidone; D000068180:Aripiprazole; D004298:Dopamine