D-2 dopamine antagonist-like effects of SCH 23390 on A9 and A10 dopamine neurons.

The effects of SCH 23390 on d-amphetamine-induced suppression of A9 and A10 DA neuronal firing were determined. SCH 23390 potently reversed d-amphetamine on both A9 and A10 DA neurons. Compared to haloperidol, SCH 23390 was 5 times more potent on A9 DA neurons and 20 times more potent on A10 DA neurons. However, the magnitude of the reversal effect was greater with haloperidol than SCH 23390. In addition, haloperidol produced a further increase in firing of both A9 and A10 DA neurons after SCH 23390 maximally increased firing. It was concluded that SCH 23390 has D-2 DA antagonist-like properties, possibly mediated via an interaction at D-1 DA receptors, which may be functionally linked with D-2 DA receptors. The marked potency of SCH 23390 in reversing d-amphetamine could be due to its combined antagonist effects at 5HT2 and D-1 DA receptor sites.