Supersensitization of the oral response to SKF 38393 in neonatal 6- hydroxydopamine-lesioned rats is eliminated by neonatal 5,7- dihydroxytryptamine treatment

R Brus, RM Kostrzewa, KW Perry and RW Fuller

Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City.

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)

Volume 268, Issue 1, pp. 231-237, 01/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics