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To study the specific contribution of the D3 dopamine receptor in the generation of locomotor activity, total or partially dopamine-depleted rats were pretreated with an antisense oligodeoxynucleotide for the D3 receptor (D3R-as) and locomotor activity induced by apomorphine was measured. A 35.7% increase in locomotor activity was seen in the totally dopamine-depleted rats pretreated with the D3R-as, whereas the same antisense, caused a significantly greater increase in the locomotor response (95%) in the partially dopamine-depleted rats compared with control groups (pretreated with a control oligodeoxynucleotide or vehicle). In situ autoradiography for D3 receptors showed a 27% fall in the density of D3 receptors in the islands of Calleja compared with control animals. Our results seem to confirm that D3 receptors exert an inhibitory effect on locomotor activity, through the stimulation of both pre- and postsynaptic components.

Contralateral rotations induced by the D1-like agonist SKF 38393 in unilaterally 6-hydroxydopamine-lesioned rats were completely prevented by the administration of the D1-like antagonist SCH 23390. A similar result was obtained after intracerebroventricular administration of an antisense oligodeoxynucleotide for the D1 receptor (D1R-as). Contrariwise, administration of a D5R-as potentiated the effects of SKF 38393, showing a 60% increase in the rotational scores. Both effects were reversible upon cessation of D1R-as or D5R-as treatment and were also specific since rotational scores in rats treated with vehicle or with a randomly designed oligodeoxynucleotide were not modified. These results suggest that whereas D1 receptors play a facilitatory role in locomotion, D5 receptors exert an inhibitory effect.