title: Factors influencing adverse skin responses in rats receiving repeated subcutaneous injections and potential impact on neurobehavior.
abstract: Repeated subcutaneous (s.c.) injection is a common route of administration in chronic studies of neuroactive compounds. However, in a pilot study we noted a significant incidence of skin abnormalities in adult male Long-Evans rats receiving daily s.c. injections of peanut oil (1.0 ml/kg) in the subscapular region for 21 d. Histopathological analyses of the lesions were consistent with a foreign body reaction. Subsequent studies were conducted to determine factors that influenced the incidence or severity of skin abnormalities, and whether these adverse skin reactions influenced a specific neurobehavioral outcome. Rats injected daily for 21 d with food grade peanut oil had an earlier onset and greater incidence of skin abnormalities relative to rats receiving an equal volume (1.0 ml/kg/d) of reagent grade peanut oil or triglyceride of coconut oil. Skin abnormalities in animals injected daily with peanut oil were increased in animals housed on corncob versus paper bedding. Comparison of animals obtained from different barrier facilities exposed to the same injection paradigm (reagent grade peanut oil, 1.0 ml/kg/d s.c.) revealed significant differences in the severity of skin abnormalities. However, animals from different barrier facilities did not perform differently in a Pavlovian fear conditioning task. Collectively, these data suggest that environmental factors influence the incidence and severity of skin abnormalities following repeated s.c. injections, but that these adverse skin responses do not significantly influence performance in at least one test of learning and memory.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: S Nikki
authors.initials: SN
authors.lastname: Levoe
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: Brenna M
authors.initials: BM
authors.lastname: Flannery
authors.affiliation: Campus Veterinary Services, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Brignolo
authors.affiliation: Comparative Pathology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Imai
authors.affiliation: Comparative Pathology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Koehne
authors.affiliation: Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA, 95817, USA.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Austin
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Bruun
authors.affiliation: Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA, 95817, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Tancredi
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA, 95616, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein
keywords: adverse skin reaction; foreign body reaction; learning and memory; neurobehavior; peanut oil; subcutaneous injection