On the involvement of the caudate-putamen, globus pallidus and substantia nigra with neuroleptic and cholinergic modification of locomotor activity

Abstract

Both haloperidol and arecoline were shown to depress spontaneous motor activity. The effect of combining the two drugs was additive only. Small doses of haloperidol consistently stimulated activity. Modification of these effects by lesions in the caudate-putamen, globus pallidus and substantia nigra were studied. A depression of activity followed by stimulation was observed after the administration of arecoline to rats with bilateral lesions of the caudate-putamen, the depressant effect being significantly reduced as compared with that in sham-operated and control animals. Lesions of the caudate-putamen did not modify the locomotor effects of haloperidol. Marked hyperactivity observed after bilateral lesions of the substantia nigra and pallidum was highly susceptible to depression by arecoline but not by haloperidol, the effects of the latter drug being respectively unmodified or abolished. Passage of an electrode to the nigra abolished the stimulant effect of haloperidol. A comparison of these results with previous work strongly suggests that the underlying mechanisms involved in the reduction of spontaneous motor activity are not the same as those involved in the production of catalepsy by neuroleptic and cholinergic drugs and therefore opposes the idea that the cataleptic effect of a drug is the extension of its depressant effect upon locomotor activity.