Behavioral effects of 5-HT2C receptor antagonism in the substantia nigra zona reticulata of the 6-hydroxydopamine-lesioned rat model of Parkinson's disease.
Overactivity of the substantia nigra zona reticulata and the medial segment of the globus pallidus are responsible for the generation of symptoms in Parkinson's disease. Reducing the activity of these regions has been shown to be a viable alternative to dopamine replacement in the symptomatic treatment of Parkinson's disease. 5-HT2C receptors in the substantia nigra zona reticulata are excitatory. In this study we have shown that intracerebral infusion of the selective 5-HT2C receptor antagonist SB 206553 (50 nmol) into the substantia nigra zona reticulata has an antiparkinsonian action in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease. SB 206553 did not affect locomotion when injected into the nonparkinsonian substantia nigra. Furthermore, we have demonstrated that systemic administration of selective 5-HT2C receptor antagonists SB 200646A (20 mg/kg) and SB 206553 (20 mg/kg) can potentiate the antiparkinsonian action of the dopamine D2 receptor agonist quinpirole in the 6-hydroxydopamine-lesioned rat. Hence, 5-HT2C receptor antagonists may be useful adjuncts to dopamine agonists in the treatment of Parkinson's disease.
Fox
S H
SH
1.124 Division of Neuroscience, School of Biological Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, United Kingdom.
Moser
B
B
Brotchie
J M
JM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008845:Microinjections; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013378:Substantia Nigra / Q000737:chemistry* / Q000502:physiology; D013565:Sympatholytics; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013565:Sympatholytics; C080864:N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea; D019257:Quinpirole; D016627:Oxidopamine; D014508:Urea; C094868:SB 206553; D007736:Kynurenic Acid