Opposite roles of D1 and D5 dopamine receptors in locomotion revealed by selective antisense oligonucleotides.
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.
Dziewczapolski
G
G
Instituto de Investigaciones Farmacológicas-CONICET, Buenos Aires, Argentina.
Menalled
L B
LB
García
M C
MC
Mora
M A
MA
Gershanik
O S
OS
Rubinstein
M
M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D007276:Injections, Intraventricular; D009043:Motor Activity / Q000502:physiology*; D016376:Oligonucleotides, Antisense; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D050641:Receptors, Dopamine D5; D012399:Rotation
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493607:Drd5 protein, rat; D016376:Oligonucleotides, Antisense; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine