title: Alternative method of oral dosing for rats.
abstract: Oral administration of drugs to laboratory rodents typically is achieved by using the gavage technique. Although highly effective, this method occasionally can cause esophageal injury as well as restraint-associated distress, particularly with repeated use. The aim of this study was to assess an alternative oral dosing method that could reduce the distress and morbidity associated with standard gavage techniques. The palatability and pharmacokinetic profile of 2 medicines approved for the treatment of Alzheimer disease, donepezil and galantamine, were investigated in male Lister hooded rats by using a syringe-feeding method and compared with results from traditional gavage administration. In addition, the stimulant nicotine was tested by using the syringe-feeding method in a separate series of experiments. Animals reliably learned to drink voluntarily from the syringe, and latency to drink decreased rapidly. The addition of donepezil, galantamine, or nicotine to sucrose had no apparent effect on the palatability of the solution, although nicotine produced aversive effects that inhibited subsequent voluntary intake. Oral bioavailability was improved by using syringe feeding with donepezil but not galantamine. Both drugs improved cognitive performance in the novel object recognition test, with similar behavioral profiles between the 2 methods of administration. Our results suggest that the syringe-feeding technique is an effective alternative oral dosing method in rats.
authors.affiliation: Centre for Cognition and Neurodegeneration, GlaxoSmithKline R&D China, Singapore. zeenatatcha@hotmail.com
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Atcha
authors.forename: Claire
authors.initials: C
authors.lastname: Rourke
authors.forename: Aveline Hp
authors.initials: AH
authors.lastname: Neo
authors.forename: Catherine Wh
authors.initials: CW
authors.lastname: Goh
authors.forename: Jean Sk
authors.initials: JS
authors.lastname: Lim
authors.forename: Chiu-Cheong
authors.initials: CC
authors.lastname: Aw
authors.forename: Edward R
authors.initials: ER
authors.lastname: Browne
authors.forename: Darrel J
authors.initials: DJ
authors.lastname: Pemberton
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000077265:Donepezil; D005702:Galantamine / Q000008:administration & dosage* / Q000494:pharmacology; D007189:Indans / Q000008:administration & dosage* / Q000494:pharmacology; D007756:Laboratory Animal Science / Q000379:methods; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D021641:Recognition, Psychology / Q000187:drug effects; D013312:Stress, Physiological; D013395:Sucrose / Q000008:administration & dosage / Q000494:pharmacology; D013594:Syringes / Q000662:veterinary; D013997:Time Factors
chemical_list: D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D005702:Galantamine; D013395:Sucrose; D009538:Nicotine; D000077265:Donepezil