Inhibition by aripiprazole of dopaminergic inputs to striatal neurons fromsubstantia nigra

Rationale: Aripiprazole (OPC-14597) elicits both dopamine D-2 agonist and a ntagonist activities on dopaminergic neurons of the ventral tegmental area and nucleus accumbens neurons, respectively. However, the electrophysiologi cal action of this drug on the striatal neurons is not clear. Objective: Th erefore, 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 neur ons with a glass microelectrode attached along a seven-barreled micropipett e, Each barrel was filled with aripiprazole, quinpirole (D2 receptor agonis t), domperidone (D2 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 n eurons 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. How ever, 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 neuron s receiving excitatory inputs from the SN.