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The Functional Observation Battery: Utility in Safety Assessment of New Molecular Entities

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Experimental Neurotoxicology Methods

Part of the book series: Neuromethods ((NM,volume 172))

Abstract

The rat functional observational battery is the regulatory standard assay for the assessment of the central nervous system prior to the first dose administration in man. This chapter describes the utility and scientific foundation for the general adoption of this technique by both European and the United States drug regulatory agencies.

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References

  1. Moser VC (2011) Functional assays for neurotoxicity testing. Toxicol Pathol 39:36–34

    PubMed  Google Scholar 

  2. Kulig BM (1996) Comprehensive neurotoxicity assessment. Environ Health Perspect 104(Suppl 2):317–322

    PubMed  PubMed Central  Google Scholar 

  3. Tilson HA (1990) Behavioral indices of neurotoxicity. Toxicol Pathol 18:96–104

    CAS  PubMed  Google Scholar 

  4. Whishaw IQ, Haun F, Kolb B (1999) Analysis of behavior in laboratory rodents. In: Windhorst U, Johansson H (eds) Modern techniques in neuroscience. Springer-Verlag, Berlin, pp 1243–1275

    Google Scholar 

  5. Weiss B, O’Donoghue J.L. (eds). (1994) Neurobehavioral toxicity: analysis and interpretation. Raven Press, New York, NY

    Google Scholar 

  6. US Environmental Protection Agency (1979) Teratogenetic/reproductive health effects. Fed Register 44:44,087, July 26, 1979

    Google Scholar 

  7. National Academy of Sciences (NAS) (1975) Principles of evaluating chemicals in the environment. National Academy of Sciences Press, Washington, D.C.

    Google Scholar 

  8. International Conference on Harmonisation (ICH) (2000) Safety pharmacology studies for human pharmaceuticals. Presentation on S7A. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S7A/Presentation/S7A_Presentation.pdf. Accessed 19 Jan 2020

  9. Mandella RC Applied neurotoxicology. In: Derelanko MJ, Hollinger MA (eds) Handbook of toxicology, 2nd edn. CRC Press, Boca Raton, FL, pp 371–400

    Google Scholar 

  10. Moser VC, Kallman MJ (2018) 6.22. Behavioral screening for toxicology and safety pharmacology. In: McQueen CA (ed) Comprehensive toxicology (3rd ed), volume 6: nervous system and behavioral toxicology. Elsevier, New York, NY, pp 409–423

    Google Scholar 

  11. Tilson HA, Mitchell CL (1984) Neurobehavioral techniques to assess the effects of chemicals on the nervous system. Ann Rev Pharmacol Toxicol 24:425–450

    CAS  Google Scholar 

  12. Tilson HA, Moser VC (1992) Comparison of screening approaches. Neurotoxicol 13:1–14

    CAS  Google Scholar 

  13. U.S. Environmental Protection Agency (1994) Final report: principles of neurotoxicity risk assessment; notice. Fed Regist 59:42,360–42,404

    Google Scholar 

  14. U.S. Environmental Protection Agency (1998) Guidelines for neurotoxicity risk assessment. Fed Regist 63(933):26,926–26,954

    Google Scholar 

  15. US Food and Drug Administration. (2016). Good laboratory practice for nonclinical laboratory studies. Proposed rule change. https://www.fda.gov/about-fda/economic-impact-analyses-fda-regulations/good-laboratory-practice-nonclinical-laboratory-studies. Fed register, docket number. FDA-2010-N-0548; notice of proposed rulemaking. https://www.regulations.gov/document?D=FDA-2010-N-0548-0088. Accessed 13 Jan 2020

  16. Lorenz MD, Coates JR, Kent M (2011) Handbook of veterinary neurology, 5th edn. Saunders (Elsevier), Philadelphia, PA

    Google Scholar 

  17. Lorenz MD, Kornegay JN (2004) Handbook of veterinary neurology, 4th edn. Saunders (Elsevier), Philadelphia, PA

    Google Scholar 

  18. Bagley RS (2005) Fundamentals of veterinary clinical neurology. Blackwell Publishing, Ltd., Oxford

    Google Scholar 

  19. U.S. Environmental Protection Agency. (1998) Guidelines for neurotoxicity risk assessment. Fed Register May 14, 1998. 63, 933; 26,926–26,954

    Google Scholar 

  20. Norton S (1978) Is behavior or morphology a more sensitive indicator of central nervous system toxicity? Environ Health Perspect 26:21–27

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Tilson HA (1987) Behavioral indices of neurotoxicity: what can be measured? Neurotoxicol Teratol 9:427–443

    CAS  PubMed  Google Scholar 

  22. Anger WK (1984) Neurobehavioral testing of chemicals: impact on recommended standards. Neurobehav Toxicol Teratol 6:147–153

    CAS  PubMed  Google Scholar 

  23. International Conference on Harmonisation (ICH) (2009) Guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals M3(R2). https://database.ich.org/sites/default/files/M3_R2__Guideline.pdf. Accessed 19 Jan 2020

  24. Whitmore E (2012) Development of FDA-regulated medical products: a translational approach, 2nd edn. Quality Press, Milwaukee, WI

    Google Scholar 

  25. Lineberry N, Berlin JA, Mansi B et al (2016) Recommendations to improve adverse event reporting in clinical trial publications: a joint pharmaceutical industry/journal editor perspective. Br Med J 355:i5078. https://doi.org/10.1136/bmj.i5078

    Article  Google Scholar 

  26. Bettge K, Kahle M, Abd El Aziz MS et al (2017) Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: a systematic analysis of published clinical trials. Diabetes Obes Metab 19:336–347

    CAS  PubMed  Google Scholar 

  27. Calabrese EJ (1991) Principles of animal extrapolation. Lewis Publishers, Inc., Chelsea, MI

    Google Scholar 

  28. Tilson HA, Cabe PA (1978) Strategy for the assessment of neurobehavioral consequences of environmental factors. Environ Health Perspect 26:287–299

    CAS  PubMed  PubMed Central  Google Scholar 

  29. MacPhail RC (1994) Behavioral analysis in neurotoxicology. In: Weiss B, O’Donoghue J (eds) Neurobehavioral toxicity: analysis and interpretation. Raven Press, New York, NY, pp 7–18

    Google Scholar 

  30. Evans HL (1989a) Behaviors in the home cage reveal toxicity: recent findings and proposals for the future. J Am Coll Toxicol 8:35–52

    Google Scholar 

  31. Evans HL (1989b) Quantitation of naturalistic behaviors. Toxicol Lett 43:345–359

    Google Scholar 

  32. Johnson RW (2002) The concept of sickness behavior: a brief chronological account of four key discoveries. Vet Immunol Immunopathol 87:443–450

    CAS  PubMed  Google Scholar 

  33. Avitsur R, Kinsey SG, Bidor K et al (2007) Subordinate social status modulates the vulnerability to the immunological effects of social stress. Psychoneuroendocrinology 32:1097–1105

    PubMed  PubMed Central  Google Scholar 

  34. Abrams PA (2009) Adaptive changes in prey vulnerability shape the response of predator populations to mortality. J Theor Biol 261:294–304

    PubMed  Google Scholar 

  35. Matzel LD, Kolata S, Light K, Sauce B (2016) The tendency for social submission predicts superior cognitive performance in previously isolated male mice. Behav Proc 134:12–21

    Google Scholar 

  36. Cooper MA, Seddighi S, Barnes AK et al (2017) Dominance status alters restraint-induced neural activity in brain regions controlling stress vulnerability. Physiol Behav 179:153–161

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Tizard I (2008) Sickness behavior, its mechanisms and significance. Anim Health Res Rev 9:87–99

    PubMed  Google Scholar 

  38. Kobrzycka A, Napora P, Pearson BL et al (2019) Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation. J Neuroinflammation 16:150. https://doi.org/10.1186/s12974-019-1544-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Irwin S (1968) Comprehensive observational assessment: 1a. A systematic quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia 13:222–257

    CAS  PubMed  Google Scholar 

  40. Moser VC (1999) Neurobehavioral screening in rodents, unit 11.2. Curr Protocols Toxicol 11(2):1–11.2.16

    Google Scholar 

  41. Baird SJS, Catalano PJ, Ryan LM et al (1997) Evaluation of effect profiles: functional observational battery outcomes. Fund Appl Toxicol 40:37–51

    CAS  Google Scholar 

  42. Becker RA, Plunkett LM, Borzelleca JF et al (2007) Tiered toxicity testing: evaluation of toxicity-based decision triggers for human health hazard characterization. Food Chem Toxicol 45:2454–2469

    CAS  PubMed  Google Scholar 

  43. Collier ZA, Gust KA, Gonzalez-Morales B et al (2006) A weight of evidence assessment approach for adverse outcome pathways. Regul Toxicol Pharmacol 75:46–57

    Google Scholar 

  44. Adeleye V, Andersen M, Clewell R et al (2015) Implementing toxicity testing in the 21st century (TT21C): making safety decisions using toxicity pathways, and progress in a prototype risk assessment. Toxicology 332:102–111

    CAS  PubMed  Google Scholar 

  45. National Research Council (NRC)/National Academy of Sciences (NAS) (2007) Toxicity testing in the 21st century: a vision and a strategy. The National Academy Press, Washington, D.C.

    Google Scholar 

  46. Carmichael NG, Barton HA, Boobis AR et al (2006) Agricultural chemical safety assessment: a multisector approach to the modernization of human safety requirements. Crit Rev Toxicol 36:1–7

    CAS  PubMed  Google Scholar 

  47. International Conference on Harmonisation (ICH) (2005) The non-clinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals S7B. https://database.ich.org/sites/default/files/S7B_Guideline.pdf

  48. Balls M, Amcoff P, Bremer S et al (2006) The principles of weight of evidence validation of test methods and testing strategies. The report and recommendations of ECVAM workshop 58. Altern Lab Anim 34:603–620

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Suter GW II, Cormier SM (2011) Why and how to combine evidence in environmental assessments: weighing evidence and building cases. Sci Total Environ 409:1406–1417

    CAS  PubMed  Google Scholar 

  50. Linkov I, Welle P, Loney D et al (2011) Use of multicriteria decision analysis to support weight of evidence evaluation. Risk Anal 31:1211–1225

    PubMed  Google Scholar 

  51. Chapman PM, McDonald BG, Lawrence GS (2002) Weight-of-evidence issues and frameworks for sediment quality (and other) assessments. Hum Ecol Risk Assess 8:1489–1515

    Google Scholar 

  52. Menzie C, Henning MH, Cura J et al (1996) Special report of the Massachusetts weight-of-evidence workgroup: a weight-of-evidence approach for evaluating ecological risks. Hum Ecol Risk Assess 2:277–304

    Google Scholar 

  53. Kraft AD, Aschner M, Cory-Slechta DA et al (2016) Unmasking silent neurotoxicity following developmental exposure to environmental toxicants. Neurotoxicol Teratol 55:38–44

    CAS  PubMed  Google Scholar 

  54. US Environmental Protection Agency. (1994) Office of prevention, pesticides and toxic substances. Health effects test guidelines. OPPTS 870.6200. Neurotoxicity screening battery. https://nepis.epa.gov/Exe/tiff2png.cgi/P100G6U5.PNG?-r+75+-g+7+D%3A%5CZYFILES%5CINDEX%20DATA%5C95THRU99%5CTIFF%5C00002709%5CP100G6U5.TIF. Accessed 20 Jan 2020

    Google Scholar 

  55. Parkinson C, McAuslane N, Lumley C et al (eds) (1994) CMR workshop: the timing of toxicological studies to support clinical trials. Kluwer, Boston, MA

    Google Scholar 

  56. Olson H, Betton G, Robinson D et al (2000) Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 32:56–67

    CAS  PubMed  Google Scholar 

  57. Claude J-R, Claude N (2004) Safety pharmacology: an essential interface of pharmacology and CMR workshop—animal toxicity studies: their relevance for man toxicology in the non-clinical assessment of new pharmaceuticals. Toxicol Lett 15:25–28

    Google Scholar 

  58. Fonck C, Easter A, Pietras MR et al (2015) CNS adverse effects: from functional observation battery/Irwin tests to electrophysiology. In: Pugsley MK, Curtis MJ (eds) Handbook of experimental pharmacology, Principles of safety pharmacology, vol 229. Springer-Verlag, Berlin, Heidelberg, pp 83–113

    Google Scholar 

  59. Mead AN, Amouzadeh H, Chapman K et al (2016) Assessing the predictive value of the rodent neurofunctional assessment for commonly reported adverse events in phase I clinical trials. Regul Toxicol Pharmacol 80:348–357

    PubMed  Google Scholar 

  60. Gribkoff VK, Kaczmarek LK (2017) The need for new approaches in CNS drug discovery: why drugs have failed, and what can be done to improve outcomes. Neuropharmacology 120:11–19

    CAS  PubMed  Google Scholar 

  61. Sette WF (1987) Complexity of neurotoxicological assessment. Neurotox Teratol 9:411–416

    CAS  Google Scholar 

  62. Moser VC (1990) Approaches for assessing the validity of a functional observational battery. Neurotox Teratol 12:483–488

    CAS  Google Scholar 

  63. Evans HL (1994) Neurotoxicity expressed in naturally occurring behavior. In: Weiss B, O’Donoghue J (eds) Neurobehavioral toxicity: analysis and interpretation. Raven Press, New York, NY, pp 111–135

    Google Scholar 

  64. Hartun T (2017) Food for thought … thresholds of toxicological concern—setting a threshold for testing below which there is little concern. ALTEX 34:331–351

    Google Scholar 

  65. Radermacher P, Haouzi P (2013) A mouse is not a rat is not a man: species-specific metabolic responses to sepsis—a nail in the coffin of murine models for critical care research? J Software Eng Res Dev 1:7. http://www.icm-experimental.com/content/1/1/7

    Google Scholar 

  66. Goldberg S (2017) The four-minute neurologic exam, 2nd edn. Medmaster, Inc., Miami, FL

    Google Scholar 

  67. Gauvin DV, Zimmermann ZJ (2019) FOB vs modified Irwin: what are we doing? J Pharmacol Toxicol Methods 97:24–28. https://doi.org/10.1016/j.vascn.2019.02.008

    Article  CAS  PubMed  Google Scholar 

  68. Ringblom J, Törnqvist E, Ove HS et al (2017) Assigning ethical weights to clinical signs observed during toxicity testing. ALTEX 34(148):156

    Google Scholar 

  69. Authier S, Arezzo J, Pouliot M et al (2019) EEG: characteristics of drug-induced seizures in rats, dogs and non-human primates. Pharmacol Toxicol Methods 97:52–58

    CAS  Google Scholar 

  70. Carstens E, Moberg GP (2000) Recognizing pain and distress in laboratory animals. ILAR J 41:62–71. https://doi.org/10.1093/ilar.41.2.62

    Article  CAS  PubMed  Google Scholar 

  71. McElwee KJ, Hoffmann R (2002) Alopecia areata—animal models. Clin Exp Dermatol 27:410–417

    CAS  PubMed  Google Scholar 

  72. McElwee KJ, Freyschmidt-Paul P, Zöller M et al (2003) Alopecia areata susceptibility in rodent models. J Investig Dermatol Symp Proc 8:182–187

    PubMed  Google Scholar 

  73. Romagnani S (1999) Th1/Th2 cells. Inflamm Bowel Dis 5:285–294

    CAS  PubMed  Google Scholar 

  74. Mathieu M (2008) New drug development: a regulatory overview (8th Ed). Parexel International Corp, Waltham, MA

    Google Scholar 

  75. Weiss B, Reuhl K (1994) Delayed neurotoxicity: a silent toxicity. In: Chang LW (ed) Principles of neurotoxicology. Marcel Dekker, Inc., New York, NY, pp 764–784

    Google Scholar 

  76. Reuhl KR (1991) Delayed expression of neurotoxicity: the problem of silent damage. Neurotoxicology 12:341–346

    CAS  PubMed  Google Scholar 

  77. Giordano G, Costa LG (2012) Developmental neurotoxicity: some old and new issues. ISRN Toxicol 2012:814795. https://doi.org/10.5402/2012/814795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Adityanjee MKR, Thampy A (2005) The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol 28:38–49

    CAS  PubMed  Google Scholar 

  79. Verdoux H, Bourgeois M (1991) Irreversible neurologic sequelae caused by lithium. Encéphale 17:221–224

    CAS  PubMed  Google Scholar 

  80. Gauvin DV, Cheng EY, Holloway FA (1993) Recent developments in alcoholism: biobehavioral correlates. Recent Dev Alcohol 11:281–304

    CAS  PubMed  Google Scholar 

  81. McKeon A, Frye MA, Delanty N (2008) The alcohol withdrawal syndrome. J Neurol Neurosurg Psychiatry 79:854–862

    CAS  PubMed  Google Scholar 

  82. Payne LE, Gagnon DJ, Riker RR et al (2017) Cefepime-induced neurotoxicity: a systematic review. Crit Care 21:276. (Open Access)

    PubMed  PubMed Central  Google Scholar 

  83. Sioka C, Kyritsis AP (2009) Central and peripheral nervous system toxicity of common chemotherapeutic agents. Cancer Chemother Pharmacol 63:761–767

    CAS  PubMed  Google Scholar 

  84. US Food and Drug Administration (2019) FDA adds boxed warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines: FDA drug safety communication. April 30, 2019. https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-risk-serious-injuries-caused-sleepwalking-certain-prescription-insomnia

  85. van Betteray JN, Vossen JM, Coenen AM (1991) Behavioural characteristics of sleep in rats under different light/dark conditions. Physiol Behav 50:79–82

    PubMed  Google Scholar 

  86. Coenen AML, Van Hulzen ZJM, Van Luijtelaar ELJM (1983) Paradoxical sleep in the dark period of the rat: a dissociation between electrophysiological and behavioral characteristics. Behav Neural Biol 37:350–356

    CAS  PubMed  Google Scholar 

  87. Gauvin DV, Zimmermann ZJ, Dalton JA, Baird TJ, Kallman MJ (2019) CNS safety screening under ICH S7A guidelines requires observations of multiple behavioral units to assess motor function. Int J Toxicol 38(5):339–356. https://doi.org/10.1177/1091581819864836

    Article  CAS  PubMed  Google Scholar 

  88. Barclay LL, Gibson GE, Blass JP (1981) The string test: an early behavioral change in thiamine deficiency. Pharmacol Biochem Behav 14:153–157. https://doi.org/10.1016/0091-3057(81)90236-7

    Article  CAS  PubMed  Google Scholar 

  89. Combs DJ, D'Alecy LG (1987) Motor performance in rats exposed to severe forebrain ischemia: effect of fasting and 1,3-butanediol. Stroke 18:503–511. https://doi.org/10.1161/01.str.18.2.503

    Article  CAS  PubMed  Google Scholar 

  90. Modianos DT, Pfaff DW (1976) Brain stem and cerebellar lesions in female rats. I. Tests of posture and movement. Brain Res 106:31–46. https://doi.org/10.1016/0006-8993(76)90071-8

    Article  CAS  PubMed  Google Scholar 

  91. Metz G, Whishaw I (2002) Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination. J Neurosci Meth 115:169–179

    Google Scholar 

  92. Roseberry T, Kreitzer A (2017) Neural circuitry for behavioural arrest. Philos Trans R Soc Lond B Biol Sci 372:20160197. https://doi.org/10.1098/rstb.2016.0197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Weaver RJ, Valentin J-P (2019) Today’s challenges to de-risk and predict drug safety in human “mind-the-gap”. Toxicol Sci 167:307–321

    CAS  PubMed  Google Scholar 

  94. Batra VR, Schrott LM (2011) Acute oxycodone induces the pro-emetic pica response in rats. J Pharmacol Exp Ther 339:738–745. https://doi.org/10.1124/jpet.111.183343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Parker LA, Brosseau L (1990) Apomorphine-induced flavor-drug associations: a dose-response analysis by the taste reactivity test and the conditioned taste avoidance test. Pharmacol Biochem Behav 35:583–587. https://doi.org/10.1016/0091-3057(90)90294-r

    Article  CAS  PubMed  Google Scholar 

  96. Parker LA, Mechoulam R (2003) Cannabinoid agonists and antagonists modulate lithium-induced conditioned gaping in rats. Integr Physiol Behav Sci 38:133–145. https://doi.org/10.1007/BF02688831

    Article  PubMed  Google Scholar 

  97. Pyun K, Son JS, Kwon YB (2014) Chronic activation of sigma-1 receptor evokes nociceptive activation of trigeminal nucleus caudalis in rats. Pharmacol Biochem Behav 124:278–283. https://doi.org/10.1016/j.pbb.2014.06.023

    Article  CAS  PubMed  Google Scholar 

  98. Sotocinal SG, Sorge RE, Zaloum A et al (2011) The rat grimace scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions. Mol Pain 7:55. https://doi.org/10.1186/1744-8069-7-55

    Article  PubMed  PubMed Central  Google Scholar 

  99. Langford DJ, Bailey AL, Chanda ML et al (2010) Coding of facial expressions of pain in the laboratory mouse. Nat Methods 7:447–449. https://doi.org/10.1038/nmeth.1455

    Article  CAS  PubMed  Google Scholar 

  100. Sacrey LA, Whishaw IQ (2010) Development of collection precedes targeted reaching: resting shapes of the hands and digits in 1-6-month-old human infants. Behav Brain Res 214:125–129. https://doi.org/10.1016/j.bbr.2010.04.052

    Article  PubMed  Google Scholar 

  101. Cosenza ME (2014) Introduction to the study director. In: Brock WJ, Mounho B, Fu L (eds) The role of the study director in nonclinical studies: pharmaceuticals, chemicals, medical devises, and pesticides. Wiley, Hoboken, NJ, pp 1–6

    Google Scholar 

  102. Tosolini AP, Morris R (2012) Spatial characterization of the motor neuron columns supplying the rat forelimb. Neuroscience 200:19–30

    CAS  PubMed  Google Scholar 

  103. Kuypers HG (1964) The descending pathways to the spinal cord, their anatomy and function. Prog Brain Res 11:178–200

    CAS  PubMed  Google Scholar 

  104. Kuypers HGJM (1981) Anatomy of the descending pathways. In: Brookhart JM, Mountcastle VB (eds) Handbook of physiology, the nervous system, vol II. Williams and Wilkins, Baltimore, MD, pp 597–666

    Google Scholar 

  105. Porter R, Lemon RN (1993) Corticospinal function and voluntary movement. Clarendon Press, Oxford, NY

    Google Scholar 

  106. Iwaniuk AN, Whishaw IQ (2000) On the origin of skilled forelimb movements. Trends Neurosci 23:372–376

    CAS  PubMed  Google Scholar 

  107. Cenci MA, Whishaw IQ, Schallert T (2002) Animal models of neurological deficits: how relevant is the rat? Nat Rev Neurosci 3:574–578

    CAS  PubMed  Google Scholar 

  108. Campbell WW, Barohn RJ (2020) DeJong’s the neurologic examination, 8th edn. Wolters Kluwer, Philadelphia, PA

    Google Scholar 

  109. Houser MC, Tansey MG (2017) The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis 3:3. https://doi.org/10.1038/s41531-016-0002-0

    Article  PubMed  PubMed Central  Google Scholar 

  110. El Aidy S, Dinan TG, Cryan JF (2014) Immune modulation of the brain-gut microbe axis. Front Microbiol 5:146. https://doi.org/10.3389/fmicb.2014.00146

    Article  PubMed  PubMed Central  Google Scholar 

  111. Clarke G, Quigley EM, Cryan JF et al (2009) Irritable bowel syndrome: towards biomarker identification. Trends Mol Med 15:478–489

    CAS  PubMed  Google Scholar 

  112. Dantzer R, O'Connor JC, Freund GG et al (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Dunn AJ (2006) Effects of cytokines and infections on brain neurochemistry. Clin Neurosci Res 6:52–68

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Graff LA, Walker JR, Bernstein CN (2009) Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management. Inflamm Bowel Dis 15:1105–1118

    PubMed  Google Scholar 

  115. Dyer RS (1984) Cross species extrapolation and hazard identification in neurotoxicology. Neurobehav Toxicol Teratol 6:409–411

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Neurobehavioral Sciences Department, Charles River Laboratories, Inc., Mattawan, MI, USA

    David V. Gauvin

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  1. David V. Gauvin
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Correspondence to David V. Gauvin .

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  1. Departament de Ciències Fisiològiques, Institut de Neurociènces, Universitat de Barcelona, Hospitalet de Llobregat, Catalunya, Spain

    Jordi Llorens

  2. Departament de Farmacologia, Toxicologia i Química Terapèutica, Universitat de Barcelona, Barcelona, Catalunya, Spain

    Marta Barenys

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Gauvin, D.V. (2021). The Functional Observation Battery: Utility in Safety Assessment of New Molecular Entities. In: Llorens, J., Barenys, M. (eds) Experimental Neurotoxicology Methods. Neuromethods, vol 172. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1637-6_8

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