Relationship of dopamine to serotonin in the neonatal 6-OHDA rat model of Lesch-Nyhan syndrome

Rats were treated as neonates with either 6-hydroqdopamine (6 OHDA) 100 mu g or vehicle intracisternally. Upon maturation, animals receiving 6-OHDA we re assigned to four groups, with two of the four groups receiving intravent ricular 5,7-dihydroxytryptamine (5,7-DHT) 75 mu g bilaterally. At 94 days o f age, animals were injected with either SKF-38393 (3.0 mg/kg, intraperiton eally (i.p.)), a dopamine DI agonist, or m-chlorophenylpiperazine (m-CPP) ( 3.0 mg/kg, i.p.), a 5-HT2C agonist, in an attempt to evoke behaviors such a s stereotypical chewing, head-nodding, self-biting and self-mutilation. Bot h SKF-38393 and m-CPP induced the target behaviors in animals receiving 6-O HDA 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 high er sensitivity to rm-CPP. Pre-treatment with SCH-23390 in animals receiving 6 OHDA alone was effective in preventing SKF-38393-induced target behavior s, but not those induced by m-CPP. Pre-treatment with mianserin partially a ntagonized the effects of both SKF-38393 and m-CPP in these same animals. I n groups receiving both neonatal 6-OHDA and adult 5,7-DHT, mianserin was ef fective in reducing m-CPP-induced behaviors, while SCH-23390 was largely in effective. These data provide evidence of a serial relationship between the D1 and 5-HT2C receptor systems in the neostriatum of animals receiving neo natal 6-OHDA lesions. (C) 1999 Lippincott Williams & Wilkins.