Low Doses of the D2 Dopamine Receptor Blocker Nemonapride Reduce the Avoidance‐suppressing Effect of the D1 Dopamine Receptor Blocker SCH 23390 in Mice

Abstract

The combined effects of the selective D1 and D2 dopamine receptor blockers, SCH 23390 and nemonapride, respectively, on the discrete shuttle avoidance response were investigated in mice. Both SCH 23390 and nemonapride (>10 μg kg−1, s.c.) significantly suppressed the avoidance response, decreasing the response rate and the percent avoidance. The avoidance-suppressing effect of SCH 23390 (10 μg kg−1 and 30 μg kg−1) was reduced by nemonapride (1 μg kg−1 and 0·3–30 μg kg−1, respectively). However, the avoidance-suppressing effect of nemonapride (10 μg kg−1) was not reduced by SCH 23390 (0·3–30 μg kg−1). The combination of comparatively higher doses of SCH 23390 and nemonapride enhanced the avoidance-suppressing effect. The present results suggest that the selective blockade of the presynaptic D2 dopamine receptors reduces the avoidance-suppression caused by the blockade of the postsynaptic D1 dopamine receptors.