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

Abstract

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.

• Authors: S M Allen, W M Davis
• Journal: Behavioural pharmacology (Behav Pharmacol) Vol. 10 Issue 5 Pg. 467-74 (Sep 1999) ISSN: 0955-8810 [Print] England
• PMID: 10780253 (Publication Type: Journal Article)

Chemical References

• Adrenergic Agents
• Receptor, Serotonin, 5-HT2C
• Receptors, Dopamine D1
• Receptors, Serotonin
• Serotonin
• Oxidopamine
• Dopamine

Topics

• Adrenergic Agents
• Animals
• Animals, Newborn
• Brain Mapping
• Disease Models, Animal
• Dopamine (physiology)
• Female
• Lesch-Nyhan Syndrome (chemically induced, physiopathology)
• Male
• Neostriatum (drug effects, physiopathology)
• Oxidopamine
• Pregnancy
• Rats
• Rats, Sprague-Dawley
• Receptor, Serotonin, 5-HT2C
• Receptors, Dopamine D1 (drug effects, physiology)
• Receptors, Serotonin (drug effects, physiology)
• Serotonin (physiology)
• Stereotyped Behavior (drug effects, physiology)