GABA involvement in neuroleptic‐induced catalepsy

cleft or in the striatal neuropil for interaction with dopamine receptor sites. Consequently, they produce a similar response in the rotating animal model. The striatum on the side of the lesion is depleted of dopamine so that the major effect of an uptake inhibitor or of a releasing agent occurs on the intact side. Accordingly, the animal in either case rotates away from the side of greater striatal dopamine activity and towards the lesioned side. Although the rotating animal model cannot distinguish between these two classes of indirect dopamine agonists, i t nevertheless adds a dimension to the study of the 'remote' analogues of amphetamine. The efficacy of the three drugs failed to correlate with their observed potency in inhibiting dopamine uptake in vitro. Mazindol is a more potent dopamine uptake inhibitor than nomifensine or dita, the latter two being approximately equivalent. Heikkila & others (1977) found ED50 values (point of 50% inhibition of uptake), for the three drugs of 2.8, 8.5 and 7.8 x lo-' M respectively. Mazindol was indeed more potent in the rotating rat than dita but nomifensine proved equivalent to mazindol. Possibly the divergent results reflect differ. ences in drug metabolism. For example, several active metabolites of nomifensine are formed in vivo (Kruse & others, 1977), one of which is equipotent with nomifensine itself in inhibiting dopamine uptake. The dopamine uptake inhibitors we have studied also inhibit the uptake of noradrenaline and 5-hydroxy. tryptamine. Thus the possibility that these mono. amines may modulate the circling response in animals with lesions of the dopamine nigrostriatal system cannot be excluded. However, the fact that dopamine uptake inhibitors cause circling in these animals whereas desipramine and amitriptyline, potent inhibitors of noradrenalinc and 5-HT uptake, do not (Christie & Crow, 1973; Pycock & others, 1976) is consistent with the growing body of evidence relating rotational behaviour in this animal model primarily to dopamine neural systems. May 22, 1978