Supersensitization of the oral response to SKF 38393 in neonatal 6-hydroxydopamine-lesioned rats is eliminated by neonatal 5,7-dihydroxytryptamine treatment.
5-Hydroxytryptamine (5-HT) 5-HT2c receptors mediate the enhanced oral activity response to the dopamine (DA) D1 agonist, (+/-)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol (SKF 38393) in neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats. To study the possible involvement of 5-HT fibers on this process, the effect of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) was determined. Rats were treated at 3 days after birth with desipramine (20 mg/kg i.p., base) 1 hr before intracerebroventricular vehicle, 6-OHDA (134 micrograms, base) and/or 5,7-DHT (50 micrograms, base). Oral activity was observed at 7 weeks and later. In neonatal 6-OHDA-lesioned rats oral activity dose-effect responses were increased by SKF 38393, 1-(3-chlorophenyl)-piperazine (m-CPP) and pilocarpine-respective DA D1, 5-HT2c and muscarinic receptor agonists. Rats treated neonatally with 5,7-DHT had agonist-induced responses resembling that of the saline control group. However, in rats treated neonatally with both 5,7-DHT and 6-OHDA, oral activity responses were reduced at nearly all doses of SKF 38393 and pilocarpine vs. that of the 6-OHDA group. The response of the 5,7-DHT + 6-OHDA group to m-CPP was reduced at only the 1.0 mg/kg dose. Of a variety of stereotyped behaviors that were observed in separate test sessions, m-CPP-induced grooming activity was less in the 5,7-DHT + 6-OHDA group vs. the 6-OHDA group.(ABSTRACT TRUNCATED AT 250 WORDS)
Brus
R
R
Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City.
Kostrzewa
R M
RM
Perry
K W
KW
Fuller
R W
RW
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D009055:Mouth; D018727:Muscarinic Antagonists; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016627:Oxidopamine; D010862:Pilocarpine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D018727:Muscarinic Antagonists; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D010862:Pilocarpine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; C015068:1-(3-chlorophenyl)piperazine