D-3 receptor knockdown through antisense oligonucleotide administration supports its inhibitory role in locomotion

TO study the specific contribution of the D-3 dopamine receptor in the gene ration of locomotor activity, total or partially dopamine-depreted rats wer e pretreated with an antisense oligodeoxynucleotide for the D-3 receptor (D 3R-as) and locomotor activity induced by apomorphine was measured. A 35.7% increase in locomotor activity was seen in the totally dopamine-depleted ra ts pretreated with the D3R-as, whereas the same antisense, caused a signifi cantly greater increase in the locomotor response (95%) in the partially do pamine-depleted rats compared with control groups (pretreated with a contro l oligodeoxynucleotide or vehicle). In situ autoradiography for D-3 recepto rs showed a 27% fall in the density of D-3 receptors in the islands of Call eja compared with control animals. Our results seem to confirm that D-3 rec eptors exert an inhibitory effect on locomotor activity, through the stimul ation of both pre- and postsynaptic components. (C) 1999 Lippincott William s & Wilkins.