Supersensitized oral responses to a serotonin agonist in neonatal 6-OHDA-treated rats.
Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with supersensitization of the dopamine D1 agonist induction of oral activity. The present study was conducted to determine whether induced oral responses to serotonin (5-HT) agonists would be similarly altered in this rat model. At 3 days after birth, rats received desipramine HCl (20 mg/kg, IP) 1 h before 6-OHDA HBr (100 micrograms in each lateral ventricle) or saline-ascorbic acid (0.1%) vehicle. At approximately 9 mo, rats were challenged with the mixed 5-HT1C and 5-HT2 receptor agonist, m-chlorophenylpiperazine diHCl (m-CPP 2HCl; 0.30-6.0 mg/kg, IP) and were then observed for 1 min every 10 min over a 60-min period. m-CPP induced oral activity in both the vehicle and 6-OHDA groups, with the responses of the 6-OHDA group being much greater. An m-CPP dose of 3.0 mg/kg produced a maximal response of 63.6 +/- 3.2 oral movements in the 6-OHDA group. A bell-shaped response curve was obtained, with lower and higher doses of m-CPP producing less of an effect. Attenuation of the m-CPP-induced response by the 5-HT receptor antagonist, mianserin HCl (1.0 mg/kg, IP, 30 min before m-CPP), indicates that the m-CPP effect is receptor mediated. These findings demonstrate that neonatal 6-OHDA treatment produces ontogenic long-lived supersensitization of a 5-HT receptor system in rats.
Gong
L
L
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614-0577.
Kostrzewa
R M
RM
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004351:Drug Resistance; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D005260:Female; D016627:Oxidopamine / Q000633:toxicity*; D010879:Piperazines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology
D010879:Piperazines; D011985:Receptors, Serotonin; D016627:Oxidopamine; C015068:1-(3-chlorophenyl)piperazine