title: A method for reliable voluntary oral administration of a fixed dosage (mg/kg) of chronic daily medication to rats.
abstract: Stress can influence a number of physiological processes including adult neurogenesis, metabolism, cardiovascular function, immune function, neurophysiological function, endocrine function and inflammatory processes following injury. In testing drugs which may be used to treat various diseases or injuries, reducing stress associated with chronic drug delivery to animal models should then be an imperative, which led us to design a reliable voluntary oral drug delivery method. Various drug combinations were tested versus vehicle controls in four different rat stocks or strains (Wistar, Fisher, Long Evans and Sprague Dawley) with our voluntary oral delivery system. Oral medications were placed into a store-bought sugar cookie dough ball (~4 g), thoroughly integrating the dry drugs with the dough. This method has worked consistently to deliver the medication (complete ingestion) in four different stocks or strains of rats, with reliabilities ranging from 98.6% to 100%. The percentage of rats in each stock or strain that have at any time during the study had incomplete ingestion of the drugs ranged from 1% in Sprague Dawley, approximately 4% in Wistar and Fisher, to approximately 16% in Long Evans. Both serum and brain samples were analysed for high-performance liquid chromatography (HPLC) detection of one of our administered drugs: 5 mg/kg fluoxetine. HPLC analysis shows that serum levels are detectable 2-4 h after ingestion, but not 24 h after ingestion. Brain samples however, showed detectable levels of both fluoxetine and norfluoxetine more than a week following ingestion of a single dose, with higher norfluoxetine levels seen following a month of daily administered drugs.
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University, 3640 Colonel Glenn Highway, Dayton, Ohio 45435, USA. Adrian.corbett@wright.edu
authors.forename: Adrian
authors.initials: A
authors.lastname: Corbett
authors.forename: Audrey
authors.initials: A
authors.lastname: McGowin
authors.forename: Scott
authors.initials: S
authors.lastname: Sieber
authors.forename: Tiffany
authors.initials: T
authors.lastname: Flannery
authors.forename: Bethany
authors.initials: B
authors.lastname: Sibbitt
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed / Q000032:analysis*; D000818:Animals; D021461:Animals, Outbred Strains; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods* / Q000662:veterinary; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000032:analysis* / Q000097:blood; D008297:Male; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010865:Pilot Projects; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood; D013045:Species Specificity; D013997:Time Factors
chemical_list: D004338:Drug Combinations; D005473:Fluoxetine; D004364:Pharmaceutical Preparations; D017367:Selective Serotonin Reuptake Inhibitors; C036139:norfluoxetine