title: No alterations in the performance of two interval timing operant tasks after alpha-difluoromethylornithine (DFMO)-induced cerebellar stunting.
abstract: The cerebellum is critically involved in temporal processes in the millisecond range and may be involved in longer time estimations (i.e. in the seconds range). Estimates in the millisecond range are impaired after developmentally induced cerebellar alterations, however, little is known about the effects of similar alterations on longer timing performance. Appropriately timed DFMO treatment reliably causes cerebellar stunting in rats, however, its effects on temporal estimation performance are unknown. Here, male and female Sprague-Dawley rats were treated with subcutaneous injections of 500 mg/kg DFMO on postnatal days 5-12, causing a 10% cerebellar weight reduction at adulthood. As adults, subjects were tested under one of two paradigms - a differential reinforcement of low response rate (DRL) task requiring that subjects withhold a lever press response for 10-14 s or a temporal response differentiation (TRD) task requiring that subjects maintain a lever press response for 10-14 s. Training and steady-state performance of the DRL and TRD tasks were not significantly altered by DFMO treatment. Performance after acute challenges with two dopaminergic agonists (2.00-7.50 mg/kg methylphenidate and 0.10-1.00 mg/kg d-amphetamine) was measured after which all subjects underwent behavioral extinction. Generally, performance after methylphenidate and d-amphetamine was similar in control and DFMO-treated rats and DFMO treatment had no differential effects on performance during extinction. These results support findings from an earlier study [Ferguson SA, Paule MG, Holson RR. Neonatal dexamethasoneon day 7 in rats causes behavioral alterations reflective of hippocampal, but not cerebellar, deficits. Neurotoxicol Teratol, 2001; 23:57-69] indicating that developmental cerebellar stunting has few effects on time estimation within the range of seconds.
authors.affiliation: Neurobehavioral Teratology Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, HFT-132, 3900 NCTR Road, Jefferson, AR 72079, USA. sferguson@nctr.fda.gov
authors.forename: S A
authors.initials: SA
authors.lastname: Ferguson
authors.forename: A M
authors.initials: AM
authors.lastname: Cada
authors.forename: E P
authors.initials: EP
authors.lastname: Gray
authors.forename: M G
authors.initials: MG
authors.lastname: Paule
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001245:Association Learning / Q000187:drug effects; D001931:Brain Mapping; D002531:Cerebellum / Q000187:drug effects*; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology; D009949:Orientation / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013998:Time Perception / Q000187:drug effects*
chemical_list: D008774:Methylphenidate; D003907:Dexamethasone; D003913:Dextroamphetamine; D000518:Eflornithine