Pharmacological and behavioral effects of D1 dopamine antagonists

This work includes the effects of SCH 23390 and related benzazepines on behavior and attempts to relate these effects to their D1 dopamine antagonist action. Effects on conditioned avoidance responding (CAR) in rats were studied under the same conditions in which in vivo binding of the radioiodinated D1 specific benzazepine 125I-SCH 38840 was measured. It was found that there is very close agreement between the time-course for antagonism of CAR and for in vivo displacement of 125I-SCH 38840 from rat striatum. The effect of SCH 23390 in CAR in monkeys was compared with standard anti-psychotics and although its oral potency was reasonable, its duration was very short (1-2 hours at 5 times its minimal effective dose for statistically significant reduction of avoidance). It is concluded from this and prior work that SCH 23390 and other D1 specific benzazepines inhibit CAR at the same doses that bind to D1 receptors in the CNS and that D1 specific antagonists are behaviorally effective at doses that do not produce D2 receptor effects (e.g. increased plasma prolactin levels, catalepsy).