D3 receptor knockdown through antisense oligonucleotide administration supports its inhibitory role in locomotion.
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.
Menalled
L B
LB
Instituto de Investigaciones Farmacológicas-CONICET, Buenos Aires, Argentina.
Dziewczapolski
G
G
Garcia
M C
MC
Rubinstein
M
M
Gershanik
O S
OS
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001345:Autoradiography; D001665:Binding Sites; D018491:Dopamine Agonists / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D020670:Islands of Calleja / Q000378:metabolism / Q000502:physiology; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D009841:Oligonucleotides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors
D018759:Adrenergic Uptake Inhibitors; D016375:Antisense Elements (Genetics); D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D009841:Oligonucleotides; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012110:Reserpine; D001058:Apomorphine