OPPOSITE ROLES OF D1 AND D5 DOPAMINE-RECEPTORS IN LOCOMOTION REVEALEDBY SELECTIVE ANTISENSE OLIGONUCLEOTIDES

CONTRALATERAL rotations induced by the D1-like agonist SKF 38393 in un ilaterally 6-hydroxydopamine-lesioned rats were completely prevented b y the administration of the D1-like antagonist SCH 23390. A similar re sult was obtained after intracerebroventricular administration of an a ntisense oligodeoxynucleotide for the D1 receptor (D1R-as). Contrariwi se, administration of a D5R-as potentiated the effects of SKF 38393, s howing a 60% increase in the rotational scores. Both effects were reve rsible upon cessation of D1R-as or DSR-as treatment and were also spec ific since rotational scores in rats treated with vehicle or with a ra ndomly designed oligodeoxynucleotide were not modified. These results suggest that whereas D1 receptors play a facilitatory role in locomoti on, D5 receptors exert an inhibitory effect.