Relationship of dopamine to serotonin in the neonatal 6-OHDA rat model of Lesch-Nyhan syndrome.
Rats were treated as neonates with either 6-hydroxydopamine (6-OHDA) 100 micrograms or vehicle intracisternally. Upon maturation, animals receiving 6-OHDA were assigned to four groups, with two of the four groups receiving intraventricular 5,7-dihydroxytryptamine (5,7-DHT) 75 micrograms bilaterally. At 94 days of age, animals were injected with either SKF-38393 (3.0 mg/kg, intraperitoneally (i.p.)), a dopamine D1 agonist, or m-chlorophenylpiperazine (m-CPP) (3.0 mg/kg, i.p.), a 5-HT2C agonist, in an attempt to evoke behaviors such as stereotypical chewing, head-nodding, self-biting and self-mutilation. Both SKF-38393 and m-CPP induced the target behaviors in animals receiving 6-OHDA alone. Animals receiving additional 5,7-DHT treatment did not show any of the target behaviors in response to SKF-38393, but exhibited a much higher sensitivity to m-CPP. Pre-treatment with SCH-23390 in animals receiving 6-OHDA alone was effective in preventing SKF-38393-induced target behaviors, but not those induced by m-CPP. Pre-treatment with mianserin partially antagonized the effects of both SKF-38393 and m-CPP in these same animals. In groups receiving both neonatal 6-OHDA and adult 5,7-DHT, mianserin was effective in reducing m-CPP-induced behaviors, while SCH-23390 was largely ineffective. These data provide evidence of a serial relationship between the D1 and 5-HT2C receptor systems in the neostriatum of animals receiving neonatal 6-OHDA lesions.
Allen
S M
SM
Department of Pharmacology, School of Pharmacy, University of Mississippi 38677, USA. sallen@olemiss.edu
Davis
W M
WM
D018663:Adrenergic Agents; D000818:Animals; D000831:Animals, Newborn; D001931:Brain Mapping; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D005260:Female; D007926:Lesch-Nyhan Syndrome / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000503:physiopathology*; D016627:Oxidopamine; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D018663:Adrenergic Agents; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; D012701:Serotonin; D016627:Oxidopamine; D004298:Dopamine