Minimal behavioral effects from developmental cerebellar stunting in young rats induced by postnatal treatment with alpha-difluoromethylornithine.
Postnatal treatment with alpha-difluoromethylornithine (DFMO), a potent inhibitor of ornithine decarboxylase, reduces polyamine levels in rats. Because polyamines are critically involved in growth and development, body and/or brain weights are often decreased by DFMO treatment. Here, rats were injected subcutaneously with 0, 250, 500, or 750 mg/kg of DFMO on postnatal days (PNDs) 5-10. Behavioral assessments included righting reflex, negative geotaxis, forelimb hanging, open field activity, and rotarod performance. Additionally, day of eye opening was recorded and on PND 28, whole and regional brain weights were measured. Cerebellar/whole-brain ratio was decreased in a dose-dependent manner whereas frontal cortex/whole-brain ratio was increased. Eye opening was delayed to a similar extent in all treated groups whereas body weight was unaffected. alpha-difluoromethylornithine treatment had no significant effects on the assessed behaviors. These results indicate that 6 days of DFMO treatment can substantially impact cerebellar development, but this appears to have few effects on these early assessed behaviors. However, potential behavioral alterations may not be apparent until adulthood. Published by Elsevier Science Inc.
Cada
A M
AM
Division of Neurotoxicology, National Center for Toxicological Research/FDA, 72079, Jefferson, AR, USA.
Gray
E P
EP
Ferguson
S A
SA
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D002526:Cerebellar Diseases / Q000139:chemically induced*; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development*; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005552:Forelimb / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D065108:Ornithine Decarboxylase Inhibitors; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D000518:Eflornithine