Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Safety and efficacy of buprenorphine for analgesia in laboratory mice and rats

Abstract

Buprenorphine is a long-acting opiate with a high therapeutic index. The authors review the pharmacology, toxicity, analgesic effects and delivery of buprenorphine for use in laboratory mice and rats. Buprenorphine-based analgesic therapy has a substantial record of safety, and there is growing evidence of its effectiveness for treating post-operative pain. Nonetheless, more research is needed to determine optimal delivery systems and analgesic regimens for pain therapy in laboratory animals.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Cowan, A., Lewis, J.W. & Macfarlane, I.R. Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. Br. J. Pharmacol. 60, 537–545 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cowan, A., Doxey, J.C. & Harry, E.J. The animal pharmacology of buprenorphine, an oripavine analgesic agent. Br. J. Pharmacol. 60, 547–54 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Orwin, J.M., Orwin, J. & Price, M. A double blind comparison of buprenorphine and morphine in conscious subjects following administration by the intramuscular route. Acta Anaesthesiol. Belg. 27, 171–181 (1976).

    CAS  PubMed  Google Scholar 

  4. Campbell, N.D. & Lovell, A.M. The history of the development of buprenorphine as an addiction therapeutic. Ann. N Y Acad. Sci. 1248, 124–139 (2012).

    Article  CAS  PubMed  Google Scholar 

  5. Farris, H.E. Effects of indomethacin and buprenorphine analgesia on the postoperative recovery of mice. J. Am. Assoc. Lab. Anim. Sci. 47, 8 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Stokes, E.L., Flecknell, P.A. & Richardson, C.A. Reported analgesic and anaesthetic administration to rodents undergoing experimental surgical procedures. Lab. Anim. 43, 149–154 (2009).

    Article  CAS  PubMed  Google Scholar 

  7. Cowan, A. Buprenorphine: new pharmacological aspects. Int. J. Clin. Pract. Suppl. 113, 3–8 (2003).

    Google Scholar 

  8. Roughan, J.V. & Flecknell, P.A. Buprenorphine: a reappraisal of its antinociceptive effects and therapeutic use in alleviating post-operative pain in animals. Lab. Anim. 36, 322–343 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Gades, N.M., Danneman, P.J., Wixson, S.K. & Tolley, E.A. The magnitude and duration of the analgesic effect of morphine, butorphanol, and buprenorphine in rats and mice. Contemp. Top. Lab. Anim. Sci. 39, 8–13 (2000).

    CAS  PubMed  Google Scholar 

  10. Karas, A. Postoperative analgesia in the laboratory mouse, Mus musculus. Lab. Anim. (NY) 31, 1–4 (2002).

    Google Scholar 

  11. Richardson, C.A. & Flecknell, P.A. Anesthesia and post-operative analgesia following experimental surgery in laboratory rodents: are we making progress? Altern. Lab. Anim. 33, 119–127 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Martin, W.R., Eades, C.G., Thompson, J.A., Huppler, R.E. & Gilbert, P.E. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J. Pharmacol. Exp. Ther. 197, 517–532 (1976).

    CAS  PubMed  Google Scholar 

  13. Virk, M.S., Arttamangkul, S., Birdsong, W.T. & Williams, J.T. Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J. Neurosci. 29, 7341–7348 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tallarida, R.J., Cowan, A. & Raffa, R.B. On deriving the dose-effect relation of an unknown second component: an example using buprenorphine preclinical data. Drug Alcohol Depend. 109, 126–129 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Raffa, R.B. & Ding, Z. Examination of the preclinical antinociceptive efficacy of buprenorphine and its designation as full- or partial-agonist. Acute Pain 9, 145–152 (2007).

    Article  CAS  Google Scholar 

  16. Yassen, A., Olofsen, E., Kan, J., Dahan, A. & Danhof, M. Pharmacokinetic-pharmacodynamic modeling of the effectiveness and safety of buprenorphine and fentanyl in rats. Pharm. Res. 25, 183–193 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Meyer, M.R. & Maurer, H.H. Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse. Pharmacogenomics 12, 215–233 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. Gopal, S., Tzeng, T.B. & Cowan, A. Characterization of the pharmacokinetics of buprenorphine and norbuprenorphine in rats after intravenous bolus administration of buprenorphine. Eur. J. Pharm. Sci. 15, 287–293 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Pontani, R.B., Vadlamani, N.L. & Misra, A.L. Disposition in the rat of buprenorphine administered parenterally and as a subcutaneous implant. Xenobiotica 15, 287–297 (1985).

    Article  CAS  PubMed  Google Scholar 

  20. Yu, S. et al. Pharmacokinetics of buprenorphine after intravenous administration in the mouse. J. Am. Assoc. Lab. Anim. Sci. 45, 12–16 (2006).

    CAS  PubMed  Google Scholar 

  21. Brown, S.M., Holtzman, M., Kim, T. & Kharasch, E.D. Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active. Anesthesiology 115, 1251–1260 (2011).

    Article  CAS  PubMed  Google Scholar 

  22. Heel, R.C., Brogden, R.N., Speight, T.M. & Avery, G.S. Buprenorphine: a review of its pharmacological properties and therapeutic efficacy. Drugs 17, 81–110 (1979).

    Article  CAS  PubMed  Google Scholar 

  23. Ponsoda, X. et al. The effects of buprenorphine on the metabolism of human hepatocytes. Toxicol. in Vitro. 5, 219–224 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. Berson, A. et al. Mechanisms for experimental buprenorphine hepatotoxicity: major role of mitochondrial dysfunction versus metabolic activation. J. Hepatol. 34, 261–269 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Kugawa, F., Arae, K., Ueno, A. & Aoki, M. Buprenorphine hydrochloride induces apoptosis in NG108-15 nerve cells. Eur. J. Pharmacol. 347, 105–112 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Ferland, C., Veilleux-Lemieux, D. & Vachon, P. Effects of buprenorphine on intracerebral collagenase-induced hematoma in Sprague-Dawley rats. J. Am. Assoc. Lab. Anim. Sci. 46, 13–16 (2007).

    CAS  PubMed  Google Scholar 

  27. Yulug, B., Cam, E., Yildiz, A. & Kilic, E. Buprenorphine does not aggravate ischemic neuronal injury in experimental focal cerebral ischemia. J. Neuropsychiatry Clin. Neurosci. 19, 331–334 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Kalliokoski, O. et al. The effect of voluntarily ingested buprenorphine on rats subjected to surgically induced global cerebral ischaemia. In Vivo 24, 641–646 (2010).

    CAS  PubMed  Google Scholar 

  29. Nakamura, S., Kakinohana, M., Sugahara, K., Kinjo, S. & Miyata, Y. Intrathecal morphine, but not buprenorphine or pentazocine, can induce spastic paraparesis after a noninjurious interval of spinal cord ischemia in the rat. Anesth. Analg. 99, 1528–1531 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Wala, E.P. & Holtman, J.R. Jr. Buprenorphine-induced hyperalgesia in the rat. Eur. J. Pharmacol. 651, 89–95 (2011).

    Article  CAS  PubMed  Google Scholar 

  31. Malek, A. & Mattison, D.R. Drugs and medicines in pregnancy: the placental disposition of opioids. Curr. Pharm. Biotechnol. 12, 797–803 (2011).

    Article  CAS  PubMed  Google Scholar 

  32. Farid, W.O., Dunlop, S.A., Tait, R.J. & Hulse, G.K. The effects of maternally administered methadone, buprenorphine and naltrexone on offspring: review of human and animal data. Curr. Neuropharmacol. 6, 125–150 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Krueger, K.L. & Fujiwara, Y. The use of buprenorphine as an analgesic after rodent embryo transfer. Lab Anim. (NY) 37, 87–90 (2008).

    Article  Google Scholar 

  34. Goulding, D.R. et al. The effects of perioperative analgesia on litter size in Crl:CD1(ICR) mice undergoing embryo transfer. J. Am. Assoc. Lab. Anim. Sci. 49, 423–426 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Hutchings, D.E., Zmitrovich, A.C., Hamowy, A.S. & Liu, P.Y. Prenatal administration of buprenorphine using the osmotic minipump: a preliminary study of maternal and offspring toxicity and growth in the rat. Neurotoxicol. Teratol. 17, 419–423 (1995).

    Article  CAS  PubMed  Google Scholar 

  36. Robinson, S.E. & Wallace, M.J. Effect of perinatal buprenorphine exposure on development in the rat. J. Pharmacol. Exp. Ther. 298, 797–804 (2001).

    CAS  PubMed  Google Scholar 

  37. Robinson, S.E. Effects of perinatal buprenorphine and methadone exposures on striatal cholinergic ontogeny. Neurotoxicol. Teratol. 24, 137–142 (2002).

    Article  CAS  PubMed  Google Scholar 

  38. Chiang, Y.C., Hung, T.W., Lee, C.W., Yan, J.Y. & Ho, I.K. Enhancement of tolerance development to morphine in rats prenatally exposed to morphine, methadone, and buprenorphine. J. Biomed. Sci. 17, 46 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Banerjee, D. & Sarkar, N.K. Haematological changes in buprenorphine-treated mice. Folia Biol. (Krakow) 45, 157–162 (1997).

    CAS  Google Scholar 

  40. Volker, D., Bate, M., Gentle, R. & Garg, M. Oral buprenorphine is anti-inflammatory and modulates the pathogenesis of streptococcal cell wall polymer-induced arthritis in the Lew/SSN rat. Lab. Anim. 34, 423–429 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Hall, T.J., Jagher, B., Schaeublin, M. & Wiesenberg, I. The analgesic drug buprenorphine inhibits osteoclastic bone resorption in vitro, but is proinflammatory in rat adjuvant arthritis. Inflamm. Res. 45, 299–302 (1996).

    Article  CAS  PubMed  Google Scholar 

  42. Van Loveren, H., Gianotten, N., Hendriksen, C.F., Schuurman, H.J. & Van der Laan, J.W. Assessment of immunotoxicity of buprenorphine. Lab. Anim. 28, 355–363 (1994).

    Article  CAS  PubMed  Google Scholar 

  43. Hugunin, K.M., Fry, C., Shuster, K. & Nemzek, J.A. Effects of tramadol and buprenorphine on select immunologic factors in a cecal ligation and puncture model. Shock 34, 250–260 (2010).

    Article  CAS  PubMed  Google Scholar 

  44. Martucci, C., Panerai, A.E. & Sacerdote, P. Chronic fentanyl or buprenorphine infusion in the mouse: similar analgesic profile but different effects on immune responses. Pain 110, 385–392 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Swenson, J., Olgun, S., Radjavi, A., Kaur, T. & Reilly, C.M. Clinical efficacy of buprenorphine to minimize distress in MRL/lpr mice. Eur. J. Pharmacol. 567, 67–76 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lindsay, D.S. et al. Buprenorphine does not affect acute murine toxoplasmosis and is recommended as an analgesic in Toxoplasma gondii studies in mice. J. Parasitol. 91, 1488–1490 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. D'Elia, M., Patenaude, J., Hamelin, C., Garrel, D.R. & Bernier, J. No detrimental effect from chronic exposure to buprenorphine on corticosteroid-binding globulin and corticosensitive immune parameters. Clin. Immunol. 109, 179–187 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Hanson, C.E., Ruble, G.R., Essiet, I. & Hartman, A.B. Effects of buprenorphine on immunogenicity and protective efficacy in the guinea pig keratoconjunctivitis model (Sereny test). Comp. Med. 51, 224–229 (2001).

    CAS  PubMed  Google Scholar 

  49. Gueye, P.N. et al. Lack of effect of single high doses of buprenorphine on arterial blood gases in the rat. Toxicol. Sci. 62, 148–154 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Chevillard, L., Mégarbane, B., Risède, P. & Baud, F.J. Characteristics and comparative severity of respiratory response to toxic doses of fentanyl, methadone, morphine, and buprenorphine in rats. Toxicol. Lett. 191, 327–340 (2009).

    Article  CAS  PubMed  Google Scholar 

  51. Dahan, A. et al. Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. Br. J. Anaesth. 94, 825–834 (2005).

    Article  CAS  PubMed  Google Scholar 

  52. Ohtani, M., Kotaki, H., Nishitateno, K., Sawada, Y. & Iga, T. Kinetics of respiratory depression in rats induced by buprenorphine and its metabolite, norbuprenorphine. J. Pharmacol. Exp. Ther. 281, 428–433 (1997).

    CAS  PubMed  Google Scholar 

  53. Yassen, A., Olofsen, E., Kan, J., Dahan, A. & Danhof, M. Animal-to-human extrapolation of the pharmacokinetics and pharmacodynamic properties of buprenorphine. Clin. Pharmacokinet. 46, 433–447 (2007).

    Article  CAS  PubMed  Google Scholar 

  54. Adamson, T.W. et al. Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad. J. Am. Assoc. Lab. Anim. Sci. 49, 610–616 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Watson, P.J., McQuay, H.J., Bullingham, R.E., Allen, M.C. & Moore, R.A. Single-dose comparison of buprenorphine 0.3 and 0.6 mg i.v. given after operation: clinical effects and plasma concentration. Br. J. Anaesth. 54, 37–43 (1982).

    Article  CAS  PubMed  Google Scholar 

  56. Chawarski, M.C., Schottenfeld, R.S., O'Connor, P.G. & Pakes, J. Plasma concentrations of buprenorphine 24 to 72 hours after dosing. Drug Alcohol Depend. 55, 157–163 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Yassen, A., Olofsen, E., Dahan, A. & Danhof, M. Pharmacokinetic-Pharmacodynamic modeling of the antinociceptive effect of buprenorphine and fentanyl in rats: Role of receptor equilibration kinetics. J. Pharmacol. Exp. Ther. 313, 1136–1149 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Liu, K.S. et al. Novel depots of buprenorphine have a long-acting effect for the management of physical dependence to morphine. J. Pharm. Pharmacol. 58, 337–344 (2006).

    CAS  PubMed  Google Scholar 

  59. Christoph, T. et al. Broad analgesic profile of buprenorphine in rodent models of acute and chronic pain. Eur. J. Pharmacol. 507, 87–98 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Canta, A. et al. Continuous buprenorphine delivery effect in streptozotocine-induced painful diabetic neuropathy in rats. J. Pain 10, 961–968 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Tubbs, J.T. et al. Effects of buprenorphine, meloxicam, and flunixin meglumine as postoperative analgesia in mice. J. Am. Assoc. Lab. Anim. Sci. 50, 185–191 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Jablonski, P., Howden, B.O. & Baxter, K. Influence of buprenorphine analgesia on post-operative recovery in two strains of rats. Lab. Anim. 35, 213–222 (2001).

    Article  CAS  PubMed  Google Scholar 

  63. Bourque, S.L., Adams, M.A., Nakatsu, K. & Winterborn, A. Comparison of buprenorphine and meloxicam for postsurgical analgesia in rats: effects on body weight, locomotor activity, and hemodynamic parameters. J. Am. Assoc. Lab. Anim. Sci. 49, 617–622 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Brennan, M.P., Sinusas, A.J., Horvath, T.L., Collins, J.G. & Harding, M.J. Correlation between body weight changes and postoperative pain in rats treated with meloxicam or buprenorphine. Lab Anim. (NY) 38, 87–93 (2009).

    Article  Google Scholar 

  65. Gillingham, M.B., Clarke, M.D., Dahly, E.M., Krugner-Higby, L.A. & Ney, D.M. A comparison of two opioid analgesics for relief of visceral pain induced by intestinal resection in rats. Contemp. Top. Lab. Anim. Sci. 40, 21–26 (2001).

    CAS  PubMed  Google Scholar 

  66. Matsumiya, L.C. et al. Using the Mouse Grimace Scale to reevaluate the efficacy of postoperative analgesia in laboratory mice. J. Am. Assoc. Lab. Anim. Sci. 51, 42–49 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. McKeon, G.P. et al. Analgesic effects of tramadol, tramadol-gabapentin, and buprenorphine in an incisional model of pain in rats (Rattus norvegicus). J. Am. Assoc. Lab. Anim. Sci. 50, 192–197 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Chappell, M.G., Koeller, C.A. & Hall, S.I. Differences in postsurgical recovery of CF1 mice after intraperitoneal implantation of radiotelemetry devices through a midline or flank surgical approach. J. Am. Assoc. Lab. Anim. Sci. 50, 227–237 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Karas, A.Z. Barriers to assessment and treatment of pain in laboratory animals. Lab. Anim. (NY) 35, 38–45 (2006).

    Article  Google Scholar 

  70. Cooper, D.M., Hoffman, W., Wheat, N. & Lee, H.Y. Duration of effects on clinical parameters and referred hyperalgesia in rats after abdominal surgery and multiple doses of analgesia. Comp. Med. 55, 344–353 (2005).

    CAS  PubMed  Google Scholar 

  71. Stewart, L.S. & Martin, W.J. Influence of postoperative analgesics on the development of neuropathic pain in rats. Comp. Med. 53, 29–36 (2003).

    CAS  PubMed  Google Scholar 

  72. Biaha, M.D. & Leon, L.R. Effects of indomethacin and buprenorphine analgesia on the postoperative recovery of mice. J. Am. Assoc. Lab. Anim. Sci. 47, 8–19 (2008).

    Google Scholar 

  73. Bomzon, A. Are repeated doses of buprenorphine detrimental to postoperative recovery after laparotomy in rats? Comp. Med. 56, 114–118 (2006).

    CAS  PubMed  Google Scholar 

  74. Guarnieri, M., Carson, B.S., Khan, A., Penno, M. & Jallo, G.I. Flexible versus rigid catheters for chronic administration of exogenous agents into central nervous system tissues. J. Neurosci. Methods 144, 147–152 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Curtin, L.I. et al. Evaluation of buprenorphine in a post-operative pain model in rats. Comp. Med. 59, 60–71 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Jessen, L., Christensen, S. & Bjerrum, O.J. The antinociceptive efficacy of buprenorphine administered through the drinking water of rats. Lab. Anim. 41, 185–96 (2007).

    Article  CAS  PubMed  Google Scholar 

  77. Leach, M.C., Forrester, A.R. & Flecknell, P.A. Influence of preferred foodstuffs on the antinociceptive effects of orally administered buprenorphine in laboratory rats. Lab. Anim. 44, 54–58 (2010).

    Article  CAS  PubMed  Google Scholar 

  78. van Loo, P.L. et al. Analgesics in mice used in cancer research: reduction of discomfort? Lab. Anim. 31, 318–325 (1997).

    Article  CAS  PubMed  Google Scholar 

  79. Kalliokoski, O., Jacobsen, K.R., Hau, J. & Abelson, K.S. Serum concentrations of buprenorphine after oral and parenteral administration in male mice. Vet. J. 187, 251–254 (2011).

    Article  CAS  PubMed  Google Scholar 

  80. Goldkuhl, R., Jacobsen, K.R., Kalliokoski, O., Hau, J. & Abelson, K.S. Plasma concentrations of corticosterone and buprenorphine in rats subjected to jugular vein catheterization. Lab. Anim. 44, 337–343 (2010).

    Article  CAS  PubMed  Google Scholar 

  81. Park, I. et al. Buprederm, a new transdermal delivery system of buprenorphine: pharmacokinetic, efficacy and skin irritancy studies. Pharm. Res. 25, 1052–1062 (2008).

    Article  CAS  PubMed  Google Scholar 

  82. Yun, M.H., Jeong, S.W., Pai, C.M. & Kim, S.O. Pharmacokinetic-pharmacodynamic modeling of the analgesic effect of Buprederm in mice. Health 2, 824–831 (2010).

    Article  Google Scholar 

  83. Pontani, R.B. & Misra, A.L. A long-acting buprenorphine delivery system. Pharmacol. Biochem. Behav. 18, 471–474 (1983).

    Article  CAS  PubMed  Google Scholar 

  84. Forbes, N. et al. Morbidity and mortality rates associated with serial bleeding from the superficial temporal vein in mice. Lab Anim. (NY) 39, 236–240 (2010).

    Article  Google Scholar 

  85. Foley, P.L., Liang, H. & Crichlow, A.R. Evaluation of a sustained-release formulation of buprenorphine for analgesia in rats. J. Am. Assoc. Lab. Anim. Sci. 50, 198–204 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Hayes, K.E., Raucci, J.A. Jr., Gades, N.M. & Toth, L.A. An evaluation of analgesic regimens for abdominal surgery in mice. Contemp. Top. Lab. Anim. Sci. 39, 18–23 (2000).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Guarnieri.

Ethics declarations

Competing interests

The authors declare competing financial interests. Funding to support this work was obtained from the biotechnology and economic development programs of Maryland Technology Development Corporation (TEDCO) and Maryland Industrial Partnerships (MIPS) and from Bamvet Laboratories, Inc. P.Z. is a paid consultant for Bamvet and is supported by a Johns Hopkins Medical Research Fellowship. M.G. holds a significant financial interest in Bamvet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guarnieri, M., Brayton, C., DeTolla, L. et al. Safety and efficacy of buprenorphine for analgesia in laboratory mice and rats. Lab Anim 41, 337–343 (2012). https://doi.org/10.1038/laban.152

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/laban.152

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing