S(+)APOMORPHINES - SELECTIVE-INHIBITION OF EXCITATORY EFFECTS OF DOPAMINE INJECTED INTO THE LIMBIC SYSTEM OF THE RAT

Dopamine (DA) injected unilaterally into the corpus striatum of the brain of the rat after pretreatment with a monoamine oxidase inhibitor, induced contralateral deviation of the head (ED50 = 23 .mu.g). DA administered similarly into the nucleus accumbens septi, induced strong locomotor arousal effects (ED50 = 32 .mu.g), as reported by others. Systemic administration of the S(+) isomers of apomorphine (APO) and its N-n-propyl analog (NPA) had no significant action on the effects on posture of DA given intrastriatally, even in large doses. In striking contrast, both agents selectively inhibited the locomotor-arousal effects of DA injected into the accumbens, but (+)NPA was 7 times more potent (ED50 = 0.5 mg/kg vs. 16 .mu.g of DA) and its effects lasted for about 70 min. The dose-effect curves for (+)NPA against 2 doses of DA demonstrated parallel, lateral displacement, indicating a competitive interaction. Enantiomers and analogs of apomorphine, and especially S(+)N-propylnorapomorphine, have potent antidopaminergic actions that may be selective for limbic areas of the forebrain.