Abnormal
involuntary movements (AIMs, stereotyped or dyskinetic movements) were induced with different
dopamine mimetics in rat, cat, and monkey. In the rat only stereotyped movements were observed, whereas in the cat
dopamine agonists (
apomorphine) preferentially induced
dyskinesia but
dopamine/
noradrenaline uptake inhibitors (
d-amphetamine,
nomifensine) induced predominantly stereotypes;
L-dopa induced an equal, low, number of both kinds of movements in the cat. In the monkey with bilateral lesions of the nigrostriatal
dopamine pathways the AIMs could be divided into type 1
dyskinesia (behavioral), type 2
dyskinesia (oral and psychomotor), and
chorea.
GABA agonists (
progabide,
muscimol) had a biphasic action on
apomorphine stereotypes in the rat, slightly (10%-20%) augmenting these movements at low doses and antagonizing (greater than 50%) them at higher doses. As these latter doses of
progabide also antagonize
apomorphine-induced circling in rats with a unilateral lesion of the substantia nigra, it is likely that this action is exerted at or beyond the
dopamine target cell. In cats the dyskinetic movements induced by
apomorphine were abolished by
progabide. In contrast,
L-dopa-induced stereotypies were resistant to the antidyskinetic action of
progabide, and at low doses of
L-dopa an increased incidence of stereotypies was noted. In the monkey, the type 1
dyskinesia following
L-dopa and
piribedil were also relatively resistant to
progabide administration, whereas the type 2
dyskinesia and
chorea were abolished by
progabide. These studies are parallel to and support the clinical observations that dyskinetic movements following a direct action at the
dopamine receptor (
tardive dyskinesia) may be reversed by
progabide whereas those associated with dopamine neuron activity, perhaps together with noradrenergic activation (
L-dopa dyskinesia), are resistant to the antidyskinetic action of
progabide.