5-HT(2C) receptor antagonists enhance the behavioural response to dopamine D(1) receptor agonists in the 6-hydroxydopamine-lesioned rat.
Non-dopaminergic therapies are of potential interest in the treatment of Parkinson's disease given the complications associated with current dopamine-replacement therapies. In this study we demonstrate that SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3, 5-tetrahydropyrrol[2,3-f]indole) (20 mg/kg) enhanced the actions of the dopamine D(1) receptor agonist, SKF 82958 ((+)-6-chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide) (1 mg/kg), in eliciting locomotion in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease. This action was only seen following prior priming with L-DOPA (L-3, 4-dihydroxyphenylalanine). SB 206553 had no effect on rotational behaviour when given alone. 5-HT(2C) receptor antagonists may have potential as a means of reducing reliance on dopamine replacement in the treatment of Parkinson's disease.
Fox
S H
SH
School of Biological Sciences, Division of Neuroscience, Manchester Movement Disorder Laboratory, University of Manchester, Room 1.124, Oxford Road, M13 9PT, Manchester, UK.
Brotchie
J M
JM
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D016627:Oxidopamine / Q000009:adverse effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000978:Antiparkinson Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D007211:Indoles; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D007980:Levodopa; C071262:SK&F 82958; D016627:Oxidopamine; C094868:SB 206553