Behavioral effects of apomorphine isomers in the rat: selective locomotor-inhibitory effects of S(+)N-n-propylnorapomorphine.

Abstract

The optical isomers of apomorphine (APO) and N-n-propylnorapomorphine (NPA) were evaluated behaviorally in the rat. Both R(-) isomers induced motor-excitatory effects and strong stereotyped sniffing, licking, and gnawing, as has been reported previously. The S(+) isomers selectively inhibited locomotor activity and did not induce stereotypy or catalepsy. These actions of the S(+) aporphines were selective against locomotor activity stimulated by low doses of R(-) isomers. (+)NPA (ID50 = 0.2 mg/kg) was 20 times more potent than (+)APO (ID50 = 4 mg/kg) in antagonizing the locomotor arousal-inducing effects of (-)APO (at ED50 = 0.3 mg/kg). (+)NPA also inhibited spontaneous locomotor activity much more potently (ID50 = 3.0 mg/kg) than did (+)APO (ID50 greater than 50 mg/kg). Neither S(+) aporphine had a significant effect against stereotypy induced by the R(-) isomers, even at high doses (up to 30 mg/kg). Inhibition of the effects of (-)APO by (+)NPA appeared not to be due to altered uptake of (-)APO into brain. These results suggest that S(+)NPA or its congeners and analogs may have selective antidopaminergic actions in limbic rather than striatal areas of mammalian brain.