1. health and fitness
2. disease

Sprague Dawley
Origin:
Originated by R. Dawley, Sprague-Dawley Company, Madison, Wisconsin, in 1925.
A hybrid hooded male (of unknown origin) was mated to a white female (of the
Douredoure strain, probably from Wistar) and subsequently to his white female
offspring for seven successive generations. Multiple lines, developed by inbreeding,
thereafter were outbred to develop a stable, heterogeneous stock. The original
colony was closed after its development, and no new stock has been introduced
since then.
HsdHot:Holtzman®™SD®™
Originally developed by Holtzman Company in Madison, Wisconsin, from
Sprague Dawley stock in 1947. To Harlan Sprague Dawley, Inc., through
acquisition in 1986.
Hsd:Sprague Dawley®™ (CD®)
In 1950 to Charles River Laboratories and in 1955 caesarean derived. From
Charles River Laboratories, Wilmington, Massachusetts to Harlan Sprague
Dawley, Inc.
Hsd:Sprague Dawley®™SD®™
Harlan purchased the former Sprague-Dawley Company in 1980. Over the
years, many sublines of the original stock have been developed and
propagated by numerous academic institutions and commercial breeders. All
current Harlan colonies are descended directly from the original stock. In
1999, to Harlan Nederland.
Characteristics:
HsdHot:Holtzman®™SD®™ – General-purpose albino stock.
Hsd:Sprague Dawley®™(CD®) – General-purpose albino stock. A very docile,
outbred rat.
Hsd:Sprague Dawley®™SD®™ – General-purpose albino stock, becoming a standard
for contemporary toxicology research. A very docile, outbred rat. Grows more
slowly and attains a significant lower maximum body weight than the Crl:CD®BR, a
rat more commonly used in toxicology studies, but distantly related to the
Hsd:Sprague Dawley®™SD®™
• Anatomy
Strain specific differences in the vermian granular layer of albinos rats have been
described by Heinsen and Heinsen (1984). The radial width of three rows of
cuticular plates of outer hair cells, the distribution of inner hair cells along the
organ of Corti, and postnatal maturation of the middle ear were examined in rats
of the Sprague-Dawley and Lewis strains aged 0-24 days and two months (Burda
1985). Differences in heart weight and myocyte number can be found in rats of
the same strain, but obtained from different suppliers (Campbell and Gerdes,
1987). Craniofacial growth and spatial relationships during secondary palate
development has been described by Diewert (1978).
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Sprague Dawley
Anatomy and immunohistochemical study of the normal colon of SpragueDawley rats (Shetye et al, 1992). Body weight and composition have been
described by Klinger et al (1996).
• Behaviour
SD preferred saline (0,9 % NaCl) in the first 24-48 h of testing but thereafter
showed neither a preference for, nor aversion to, saline (Di Nicolantonio et al,
1983). Better maternal behaviour than Wistar rats (Jakubowski and Terkel, 1985).
The rate of acquisition of lever-pressing for electrical stimulation of the
hippocampus (HPC) was compared in Wistar and Sprague-Dawley. SpragueDawley rats initially bar-pressed at very low rates and took a median of 11 days
to self-stimulate, according to the criterion used.
Wistar rats all reached the same criterion in the first test session (Robertson et al,
1986). The lack of appetite for isotonic NaCl solution in rats of the Long-Evans
strain compared to those of the Sprague-Dawley strain is most likely related to
the failure of rats of the former strain to discriminate between water and NaCl
solution until the concentration of NaCl exceeds 0.15 M. However, at this
concentration, both strains rejected NaCl solution in favour of water. In contrast
to the results with NaCl solution, rats of the Long-Evans strain appear to have a
greater appetite for 5% glucose solution than do those of the Sprague-Dawley
strain (Fregly and Rowland, 1992). Study of behavioural heterogeneity and its
consequences for behavioural tests (Cure et al, 1992).
• Drugs
Resistant saccharine-induced carcinogenesis (Fukushima et al, 1983). Less
sensitive to acute neurotoxic effects of trimethyltin than Long-Evans (Chang et al,
1983). Morphine responses vary considerably between strains of animals and are
influenced by gonadal hormones of females, but not of males (Kasson and
George, 1984). Superficial corneal opacity with age (Bellhorn et al, 1988). LiCl
increased inositol-1-phosphate levels 1.8 to 7.4 fold in different regions of brain
of Sprague Dawley rats but only 1.2 to 1.8 fold in Han/Wistar rats (Savolainen et
al, 1990). Susceptible to the induction de urinary bladder stones by foreign
bodies, in contrast to Brattleboro (Shimamura and Strauss, 1988). Resistant to the
induction of ulcers by stress (Pare, 1989). Head width and palatal clefting are
causally related (Siegel and Mooney, 1986). Mercuric chloride (HgCl2) was
found to increase microsomal epoxide hydrolase activity in the kidneys of F344
and Sprague-Dawley rats, but the increases observed were 2- to 4-fold greater in
Sprague-Dawley rats than in F344 rats (Kroll et al, 1988). Intermediate sensitive
to the induction of squamous cell carcinomas of the tongue by 4-nitroquinoline 1oxide (Kitano et al, 1992). Description of an experimental model for selective
myocardial impairment with reduced inotropism and lusitropism after anaphylaxis
(Sun et al, 1992). Bromocriptine treatment reduced prolactin levels in both strains,
but the effect was more rapid in Holtzman SD rats than in Long-Evans rats
(Cannon et al, 1991a). F344 rats showed a smaller decrease in blood pressure
following administration of isoproterenol than did those of Sprague Dawley rats
(Caputo et al, 1992). Description of ear tumours that appear in a model of colon
carcinogenesis in rats 1,2-dimethylhydrazine (Vinas-Salas et al, 1992).
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Sprague Dawley
Sprague Dawley is particular resistant to the nephrotoxic effect of cyclosporine A
and Rapamycin, compared to LEW (intermediate sensitive) and SHR (very
sensitive) (DiJoseph et al, 1993). Sprague Dawley rats are less sensitive to
aminoglycoside-induced nephrotoxicity than F344 rats (Reinhard et al, 1991).
Pathological changes associated with the use of Tribromoethanol (Avertin) have
been described by Reid et al, 1999). The choice of anaestetic affects the data in
certain coagulation assays (Stringer and Seligman, 1996).
• Genetics
Coat colour genes
– c : albino.
Other genes are variable (outbred stock).
Hsd:Sprague Dawley®™SD®™ - Harlan Nederland
• Growth Chart
Weight (g)
400
300
M
200
F
100
0
3
4
5 6
7
8 9 10 11 12 13
Age in weeks
• Immunology
Resistant to the induction of proteinuria following treatment with the monoclonal
antibody 5-6-1, but unlike LEW and outbred Wistar, which were susceptible to
glomerular damage (Gollner et al, 1995). The Holtzman rat is especially sensitive
to Freund adjuvant induced arthritis (Bersani-Amado et al, 1990).
• Life-span and Spontaneous Disease
The median survival time was 24.5 months for virgins and 25 months for
breeders (Cameron et al, 1982). Pituitary adenomas in ageing rats (Mc Comb et
al, 1984). Pituitary gland tumours were found in 20% of the males and 39% of
the females. This relatively low incidence, compared to other Sprague Dawley
stocks, had little effect on the survival of the females (50%), due to the high
incidence (76%) of mammary gland tumours (predominantly fibroadenomas)
resulted in unscheduled sacrifices of many female. Other common neoplasms in
Hsd:Sprague-Dawley rats were benign medullary tumours (27% in males, 11% in
females), C-cell adenomas (23% in males, 28% in females), and endometrial
stromal polyps (22% in females) (Kaspareit and Rittinghausen, 1999).
Spontaneous tumours in Holtzman SD rats have been described by Schardein et
al (1968).
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Sprague Dawley
• Physiology and Biochemistry
Effects of restraint, cage transportation, anaesthesia and repeated bleeding on
plasma glucose levels have been described by Tabata et al (1998). Chronic dietinduced obesity developed in 50-60% of male Sprague-Dawley rats fed a
relatively high-calorie diet for 90 days (Levin et al, 1983).
Lean male Sprague Dawley rats acclimated to 21˚ C have suppressed brown
adipose tissue temperature responses to ventromedial hypothalamic nucleus
electrical stimulation compared with lean LE rats due to a reduced thermogenic
capacity of that tissue (Thornhill and Halvorson, 1992). The sensitivity of
Holzman SD rats for the induction of mammary tumours is associated with the
low level of serum prolactin, compared with the higher levels of prolactin in
tumour-resistant Long-Evans rats (Cannon et al, 1991b). Harderian gland
porphyrin concentrations were 1.5-fold higher in F344 male rats than in SpragueDawley male rats (Vaughan et al, 1991). A report of large differences in the
diurnal and stress corticosterone profiles between F344, LEW and SD: (1) F344
rats had significantly higher diurnal and stress corticosterone levels than SD and
LEW rats; (2) in the morning, stress corticosterone levels of SD and F344 rats
returned towards basal 1 h after cessation of the stressor, whereas stress
corticosterone levels of LEW rats had not returned to basal by this time; and (3)
in the evening, SD and F344 rats showed the expected evening rise in basal stress
corticosterone levels, whereas LEW rats failed to show this rise (Dhabhar et al,
1993).
• Reproduction
ACI male of 2 years old sired an average of 3.8 litters during a 6 months breeding
period, while Sprage Dawley rats of similar age sired an average of 0.9 litters
within the same period (Cameron et al, 1982). Gestation period: 22.39 ± .43 days
(Peters, 1986).
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Sprague Dawley
Parameters:
Hsd:Sprague Dawley®™SD®™ - Harlan Nederland
Full brochure with background data available on request.
References:
Bellhorn RW, Korte GE, Abrutyn D (1988) Spontaneous corneal degeneration in the rat. Lab. Anim.
Sci. 38, 46-50.
Bersani-Amado CA et al (1990) Comparative study of adjuvant induced arthritis in susceptible and
resistant strains of rats. I-Effect of cyclophosphamide. J. Rheumatol. 17, 149-152
Burda H (1985) Qualitative assessment of postnatal maturation of the organ of Corti in two rat
strains. Hearing Res. 17, 201-208.
Cameron TP, Lattuada CP, Kornreich MR, Tarone RE (1982) Longevity and reproductive
comparisons for male ACI and Sprague-Dawley rat aging colonies. Lab. Anim. Sci. 32, 495-499.
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Sprague Dawley
Campbell SE, Gerdes AM (1987) Regional differences in cardiac myocyte dimensions and number in
Sprague-Dawley rats from different suppliers. Proc. Soc. Exper. Biol. Med. 186, 211-217.
Cannon M, Hu L, Ye J, Lawson D (1991a) A comparison of plasma prolactin levels in young female
Long-Evans and Holtzman rats as measured by Nb2 lymphoma bioassay and radioimmunoassay.
Proc. Soc. Exp. Biol. Med. 197, 471-476.
Cannon M, Hu L, Ye J, Lawson D (1991b) Bioactivity of plasma prolactin in ovariectomized,
diethylstilbestrol-treated Long-Evans and Holtzman rats after thyrotropinreleasing hormone or
bromocriptine administration. Proc. Soc. Exp. Biol. Med. 197, 465-470.
Caputo FA, Rowland NE, Fregly MJ (1992) Angiotensin-related intakes of water and NaCl in
Fischer-344 and Sprague-Dawley rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 262, R382R388.
Chang LW, Wenger GR, McMillan DE et al (1983) Species and strain comparison of acute
neurotoxic effects of trimethyltin in mice and rats. Neurobehav. Toxicol. Teratol. 5, 337-350.
Cure M et al (1992) Behavioral heterogeneity in Sprague-Dawley rats. Physiol. Behav. 51, 771-774.
Dhabhar FS, McEwen BS, Spencer RL (1993) Stress response, adrenal steroid receptor levels and
corticosteroid-binding globulin levels – a comparison between Sprague-Dawley, Fischer 344 and
Lewis rats. Brain Res. 616, 89-98.
Di Nicolantonio R, Mendelsohn FA, Hutchinson JS (1983) Sodium chloride preference of
genetically hypertensive and normotensive rats. Am. J. Physiol. 245, R38-R44.
Diewert VM (1978) A quantitative coronal plane evaluation of craniofacial growth and spatial
relationships during secondary palate development in the rat. Arch. Oral Biol. 23, 607-629.
DiJoseph JF, Mihatsch MJ, Sehgal SN (1993) Influence of rat strain on rapamycin's kidney effects.
Transplant. Proc. 25, 714-715.
Fregly MJ, Rowland NE (1992) Comparison of preference thresholds for NaCl solution in rats of the
Sprague-Dawley and Long-Evans strains. Physiol. Behav. 51, 915-918.
Fukushima S, Aral M, Nakanowatari J, Hibino T, Okuda M, Ito N (1983) Differences in
susceptibility to sodium saccharin among various strains of rats and other animal species. Gann
74, 8–20.
Gollner D, Kawachi H, Oite T, Oka M, Nagase M, Shimizu F (1995) Strain variation in susceptibility
to the development of monoclonal- antibody 5-1-6-induced proteinuria in rats. Clin. Exp.
Immunol. 101, 341-345.
Heinsen H, Heinsen YL (1984) Strain specific differences in the vermian granular layer of albinos
rats. Acta Anat. 119, 165-175.
Jakubowski M, Terkel J (1985) Incidence of pup killing and parental behavior in virgin female and
male rats (Rattus norvegicus): Differences between Wistar and Sprague-Dawley stocks. J. Comp.
Psych. 99, 93-97.
Kaspareit J, Rittinghausen S (1999) Spontaneous neoplastic lesions in Harlan Sprague-Dawley rats.
Experimental and Toxicologic Pathology 51, 105-107.
Kasson BG, George R (1984) Endocrine influences on the actions of morphine. IV. Effects of sex and
strain. Life Sci 34, 1627-1634.
Kitano M, Hatano H, Shisa H (1992) Strain difference of susceptibility to 4-nitroquinoline 1-oxideinduced tongue carcinoma in rats. Jpn. J. Cancer Res. 83, 843-850.
Klinger MM, MacCarter GD, Boozer CN (1996) Body weight and composition in the Sprague
Dawley rat: Comparison of three outbred stocks. Lab. Anim. Sci. 46, 67-70.
Kroll DJ, Graichen ME, Leonard TB (1988) Strain difference in rat renal microsomal epoxide
hydrolase elevation after mercuric chloride treatment. Carcinogenesis 9, 193-198.
Levin BE, Triscari J, Sullivan AC (1983) Relationship between sympathetic activity and diet-induced
obesity in two rat strains. Am. J. Physiol. Regul. Integr. Comp. Physiol. 245, R364-R371.
Mc Comb DJ et al (1984) Pituitary adenomas in old Sprague-Dawley rats : a histologic ultrastructural
and immunocytochemical study. J. Nat. Cancer Inst. 73, 1143-1166.
Pare W. (1989) Strain, age, but not gender, influence ulcer severity induced by water-restraint stress.
Physiol. Behav. 45, 627-632.
Peters AG (1986) Length of gestation period on eight inbred strains and three outbred strains of rats.
Animal Technology 37, 109-112.
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Sprague Dawley
Reid WC, Carmichael KP, Srinivas S, Bryant JL (1999) Pathological changes associated with the use
of tribromoethanol (Avertin) in the Sprague Dawley rat. Lab. Anim. Sci. 49, 665-667.
Reinhard MK, Hottendorf GH, Powell ED (1991) Differences in the sensitivity of Fischer and
Sprague-Dawley rats to aminoglycoside nephrotoxicity. Toxicol. Pathol. 19, 66–71.
Robertson A, Campbell C, Milner PM, Laferriere A (1986) Rat strain differences in the acquisition of
hippocampal self-stimulation. Brain Res. Bull. 16, 369–375.
Savolainen KM, Hirvonen MR, Tarhanen J, Nelson SR, Samson FE, Pazdernik TL (1990) Changes in
cerebral inositol-1-phosphate concentrations in LiCl-treated rats: regional and strain differences.
Neurochem. Res. 15, 541-545.
Schardein JL. Fitzgerald JE, Kaump DH (1968) Spontaneous tumors in Holtzman-source rats of
various ages. Path. Vet. 5, 238-252.
Shetye JD et al (1992) Normal colon of Sprague-Dawley rats. An immunohistochemical study. Anat.
Embriol. 185, 69-76.
Shimamura T, Strauss G (1988) Reaction to vesical foreign bodies in two strains of rats. Jpn. J. Exp.
Med. 58 9-13.
Siegel MI and Mooney MP (1986) Palatal width growth rates as the genetic determinant of cleft
palate induced by vitamin A. J. Craniofacial Gen. Develop. Biol. Suppl. 2, 187-191.
Stringer SK, Seligman BE (1996) Effects of two injectable anesthetic agents on coagulation assays in
the rat. Lab. Anim. Sci. 46, 430-433.
Sun, S., Weil MH, Tang W, Gazmuri RJ, Bisera J, Greenberg SR, Kim TB (1992) Cardiac
anaphylaxis in the Sprague-Dawley rat. J. Lab. Clin. Med. 120, 589-596.
Tabata H, Kitamura T, Nagamatsu N (1998) Comparison of restraint, cage transportation, anaesthesia
and repeated bleeding on plasma glucose levels between mice and rats. Lab. Anim. 32, 142-148.
Thornhill J, Halvorson I (1992) Differences in brown adipose tissue thermogenic responses between
Long-Evans and Sprague-Dawley rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 263, R59R69.
Vaughan MK, Vaughan GM, Chenoweth PC, Menendez-Pelaez A, Rodriguez C, Chambers JP,
Hoover PA, Reiter RJ (1991) Harderian gland porphyrin, lysosomal and type II 5'-deiodinase
rhythms in Sprague-Dawley and Fischer-344 rats kept under chronic long- or short-photoperiod
conditions. Int. J. Biochem. 23, 919-924.
Vinas-Salas J, Fortuny JC, Panades J, Pinol C, Prim M, Ferminan A, Corbella G, Caldero J, Egido R
(1992) Appearance of ear tumors in Sprague-Dawley rats treated with 1,2-dimethylhydrazine
when used as a model for colonic carcinogenesis. Carcinogenesis 13, 493-495.
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