Behavior Genetics

, Volume 47, Issue 5, pp 537–551 | Cite as

Conservation of Phenotypes in the Roman High- and Low-Avoidance Rat Strains After Embryo Transfer

  • Cristóbal Río-Álamos
  • Cristina Gerbolés
  • Carles Tapias-Espinosa
  • Daniel Sampedro-Viana
  • Ignasi Oliveras
  • Ana Sánchez-González
  • Toni Cañete
  • Gloria Blázquez
  • María del Mar López
  • Carlos Baldellou
  • Pedro J. Otaegui
  • Adolf Tobeña
  • Alberto Fernández-Teruel
Original Research
First Online:
Received:
Accepted:

Abstract

The Roman high- (RHA-I) and low-avoidance (RLA-I) rat strains are bi-directionally bred for their good versus non-acquisition of two-way active avoidance, respectively. They have recently been re-derived through embryo transfer (ET) to Sprague–Dawley females to generate specific pathogen free (SPF) RHA-I/RLA-I rats. Offspring were phenotyped at generations 1 (G1, born from Sprague–Dawley females), 3 and 5 (G3 and G5, born from RHA-I and RLA-I from G2–G4, respectively), and compared with generation 60 from our non-SPF colony. Phenotyping included two-way avoidance acquisition, context-conditioned fear, open-field behaviour, novelty-seeking, baseline startle, pre-pulse inhibition (PPI) and stress-induced increase in plasma corticosterone concentration. Post-ET between-strain differences in avoidance acquisition, context-conditioned freezing and novelty-induced self-grooming are conserved. Other behavioural traits (i.e. hole-board head-dipping, novel object exploration, open-field activity, startle, PPI) differentiate the strains at G3–G5 but not at G1, suggesting that the pre-/post-natal environment may have influenced these co-segregated traits at G1, though further selection pressure along the subsequent generations (G1–G5) rescues the typical strain-related differences.

Keywords

Roman rat strains Embryo transfer Behavioural phenotyping Two-way active avoidance Stress-induced corticosterone 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

This work was supported by Grants PSI2013-41872-P (MINECO), 2014SGR-1587 (DGR), “ICREA-Academia 2013” (to A.F.-T. and A.T.). C.T.-E. is recipient of a Ph.D. FPU fellowship (FPU15/06307). I.O. is recipient of a Ph.D. FI fellowship (DGR 2014). A.S.-G. is recipient of a Ph.D. FPI fellowship.

Compliance with ethical standards

Conflict of interest

Authors Cristóbal Río-Álamos, Cristina Gerbolés, Carles Tapias-Espinosa, Daniel Sampedro-Viana, Ignasi Oliveras, Ana Sánchez-González, Toni Cañete, Gloria Blázquez, María del Mar López, Carlos Baldellou, Pedro J. Otaegui, Adolf Tobeña, and Alberto Fernández-Teruel declare that they have no conflict of interest.

Human and animal rights

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All the procedures were in accordance with the Spanish Royal Decree (RD 53/2013) for the protection of experimental animals and with the European Communities Council Directive (2010/63/EU).

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. Bignami G (1965) Selection for high rates and low rates of avoidance conditioning in the rat. Anim Behav 13:221–227CrossRefPubMedGoogle Scholar
  2. Carrasco J, Márquez C, Nadal R, Tobeña A, Fernández-Teruel A, Armario A (2008) Characterization of central and peripheral components of the hypothalamus-pituitary-adrenal axis in the inbred Roman rat strain. Psychoneuroendocrinology 33:437–445CrossRefPubMedGoogle Scholar
  3. Castanon N, Perez-Diaz F, Mormède P (1995) Genetic analysis of the relationship between behavioral and neuroendcrine traits in Roman high and low avoidances rat lines. Behav Genet 25:371–384CrossRefPubMedGoogle Scholar
  4. Del Río C, Oliveras I, Cañete T, Blázquez G, Tobeña A, Fernández- Teruel A (2014) Genetic rat models of schizophrenia-relevant symptoms. World J Neurosci 4:261–278CrossRefGoogle Scholar
  5. Denhardt DT (2017) Effect of stress on human biology: epigenetics, adaptation, inheritance, and social significance. J Cell Physiol. doi: 10.1002/jcp.25837 (Epub ahead of print)PubMedGoogle Scholar
  6. Díaz-Morán S, Palència M, Mont-Cardona C, Cañete T, Blázquez G, Martínez-Membrives E (2012) Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains. Behav Brain Res 228:203–210CrossRefPubMedGoogle Scholar
  7. Driscoll P, Bättig K (1982) Behavioural, emotional and neurochemical profiles of rats selected for extreme differences in active, two-way avoidance performance. In: Lieblich I (ed) Genetics of the brain, 1st edn. Elsevier, Amsterdam, pp 95–123Google Scholar
  8. Driscoll P, Escorihuela RM, Fernández-Teruel A, Giorgi O, Schwegler H, Steimer T (1998) Genetic selection and differential stress responses. The Roman lines/strains of rats. Ann N Y Acad Sci 851:501–510CrossRefPubMedGoogle Scholar
  9. Driscoll P, Fernández-Teruel A, Corda MG, Giorgi O, Steimer T (2009) Some guidelines for defining personality differences in rats. In: Yong-Kyu K (ed) Handbook of behavior genetics. Springer, New York, pp 281–300CrossRefGoogle Scholar
  10. Escorihuela RM, Fernández-Teruel A, Gil L, Aguilar R, Tobeña A, Driscoll P (1999) Inbred Roman high- and low- avoidance rats: differences in anxiety, novelty seeking and shuttle box behaviors. Physiol Behav 67:19–26CrossRefPubMedGoogle Scholar
  11. Esnal A, Sánchez-González A, Río-Álamos C, Oliveras I, Cañete T, Blázquez G, Tobeña A, Fernández-Teruel A (2016) Prepulse inhibition and latent inhibition deficits in Roman high-avoidance vs. Roman low-avoidance rats: modeling schizophrenia-related features. Physiol Behav 163:267–273CrossRefPubMedGoogle Scholar
  12. Estanislau C, Díaz-Morán S, Cañete T, Blázquez G, Tobeña A, Fernández-Teruel A (2013) Context-dependent differences in grooming behavior among the NIH heterogeneous stock and the Roman high-and low-avoidance rats. Neurosci Res 77:187–201CrossRefPubMedGoogle Scholar
  13. Fernández-Teruel A, Estanislau C (2016) Meanings of self-grooming depend on an inverted U-shaped function with aversiveness. Nat Rev Neurosci 17:591–592CrossRefPubMedGoogle Scholar
  14. Fernández-Teruel A, Escorihuela RM, Núñez JF, Zapata A, Boix F, Salazar W (1991) The early acquisition of two-way (shuttle-box) avoidance as an anxiety-mediated behavior: psychopharmacological validation. Brain Res Bull 6:173–176CrossRefGoogle Scholar
  15. Fernández-Teruel A, Escorihuela RM,  Gray JA, Aguilar R, Gil L, Giménez-Llort L et al (2002) A quantitative trait locus influencing anxiety in the laboratory rat. Genome Res 12:618–626CrossRefPubMedPubMedCentralGoogle Scholar
  16. Francis D, Diorio J, Liu D, Meaney MJ (1999) Nongenetic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155–1158CrossRefPubMedGoogle Scholar
  17. Garcia-Falgueras A, Castillo-Ruiz MM, Put T, Tobeña A, Fernández-Teruel A (2012) Differential hippocampal neuron density between inbred Roman high. (low anxious) and low-avoidance (high anxious) rats. Neurosci Lett 522:41–46CrossRefPubMedGoogle Scholar
  18. Giorgi O, Lecca D, Piras G, Driscoll P, Corda MG (2003a) Dissociation between mesocortical dopamine release and fear-related behaviours in two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions. Eur J Neurosci 17:2716–2726CrossRefPubMedGoogle Scholar
  19. Giorgi O, Piras G, Lecca D, Hansson S, Driscoll P, Corda MG (2003b) Differential neurochemical properties of central serotonergic transmission in Roman high- and low-avoidance rats. J Neurochem 86:422–431CrossRefPubMedGoogle Scholar
  20. Giorgi O, Piras G, Corda MG (2007) The psychogenetically selected Roman high- and low- avoidance rat lines: a model to study the individual vulnerability to drug addiction. Neurosci Biobehav Rev 31:148–163CrossRefPubMedGoogle Scholar
  21. Gómez MJ, Morón I, Torres C, Esteban FJ, De la Torre L, Cándido A, Maldonado A, Fernández-Teruel A, Tobeña A (2009) One-way avoidance acquisition and cellular density in the basolateral amygdala: strain differences in Roman high- and low- avoidance rats. Neurosci Lett 450:317–320CrossRefPubMedGoogle Scholar
  22. Greer JM, Capecchi MR (2002) Hoxb8 is required for normal groomig behavior in mice. Neuron 33:23–34CrossRefPubMedGoogle Scholar
  23. Guitart-Masip M, Giménez-Llort L, Fernández-Teruel A, Canete T, Tobena A, Ögren SO (2006) Reduced ethanol response in the alcohol-preferring RHA rats and neuropeptide mRNAs in relevant structures. Eur J Neurosci 23:531–540CrossRefPubMedGoogle Scholar
  24. Guitart-Masip M, Johansson B, Fernández-Teruel A, Tobeña A, Gimenez-Llort L (2008) Divergent effect of the selective D3 receptor agonist pd-128,907 on locomotor activity in Roman high- and low-avoidance rats: relationship to NGFI-A gene expression in the Calleja islands. Psychopharmacology 196:39–49CrossRefPubMedGoogle Scholar
  25. Kalueff AV, Stewart AM, Song C, Berridge KC, Graybiel AM, Fentress JC (2016) Neurobiology of rodent self-grooming and its value for translational neuroscience. Nat Rev Neurosci 17:45–59CrossRefPubMedGoogle Scholar
  26. Klein AB, Ultved L, Adamsen D, Santini MA, Tobeña A, Fernández-Teruel A (2014) 5-HT (2A) and mGlu2 receptor binding levels are related to differences in impulsive behavior in the Roman Low- (RLA) and High-(RHA) avoidance rat strains. Neuroscience 263:36–45CrossRefPubMedGoogle Scholar
  27. López-Aumatell R, Vicens-Costa E, Guitart-Masip M, Martínez-Membrives E, Valdar W, Johannesson M (2009a) Unlearned anxiety predicts learned fear: a comparison among heterogeneous rats and the Roman rat strains. Behav Brain Res 202:92–101CrossRefPubMedGoogle Scholar
  28. López-Aumatell R, Blázquez G, Gil L, Aguilar R, Cañete T, Giménez-Llort L (2009b) The Roman high- and low-avoidance rat strains differ in fear-potentiated startle and classical aversive conditioning. Psicothema 21:27–32PubMedGoogle Scholar
  29. Manzo L, Gómez MAJ, Callejas-Aguilera JE, Donaire R, Sabariego M, Fernández-Teruel A (2014) Relationship between ethanol preference and sensation/novelty seeking. Physiol Behav 133:53–60CrossRefPubMedGoogle Scholar
  30. Meyza KZ, Boguszewski PM, Nikolaev E, Zagrodzka J (2009) Diverse sensitivity of RHA/Verh and RLA/Verh rats to emotional and spatial aspects of a novel environment as a result of adistinct pattern of neuronal activation in the fear/anxiety circuit. Behav Genet 39:48–61CrossRefPubMedGoogle Scholar
  31. Moreno M, Cardona D, Gómez MJ, Sánchez-Santed F, Tobeña A, Fernández-Teruel A (2010) Impulsivity characterization in the Roman high- and low-avoidance rat strains: behavioral and neurochemical differences. Neuropsychopharmacology 35:1198–1208CrossRefPubMedPubMedCentralGoogle Scholar
  32. Oliveras I, Río-Álamos C, Cañete T, Blázquez G, Martínez-Membrives E, Giorgi O, Corda MG, Tobeña A, Fernández-Teruel A (2015) Prepulse inhibition predicts spatial working memory performance in the inbred Roman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: relevance for studying pre-attentive and cognitive anomalies in schizophrenia. Front Behav Neurosci 9:213CrossRefPubMedPubMedCentralGoogle Scholar
  33. Río-Álamos C, Oliveras I, Cañete T, Blázquez G, Martínez-Membrives E, Tobeña A, Fernández-Teruel A (2015) Neonatal handling decreases unconditioned anxiety, conditioned fear, and improves two-way avoidance acquisition: a study with inbred Roman high (RHA-I)- and low-avoidance (RLA-I) rats of both sexes. Front Behav Neurosci 9:174CrossRefPubMedPubMedCentralGoogle Scholar
  34. Rosas JM, Callejas-Aguilera JE, Escarabajal MD, Gomez MJ, De la Torre L, Agüero A (2007) Successive negative contrast effect in instrumental runway behaviour: a study with Roman high- (RHA) and Roman low- (RLA) avoidance rats. Behav Brain Res 185:1–8CrossRefPubMedGoogle Scholar
  35. Sabariego M, Gómez MJ, Morón I, Torres C, Fernández-Teruel A, Tobena A et al (2011) Differential gene expression between inbred Roman high- (RHA-I) and low- (RLA-I) avoidance rats. Neurosci Lett 504:265–270CrossRefPubMedGoogle Scholar
  36. Sanna F, Piludu MA, Corda MG, Melis MR, Giorgi O, Argiolas A (2015) Involvement of dopamine in the differences in sexual behaviour between Roman high and low avoidance rats: an intracerebral microdialysis study. Behav Brain Res 281:177–186CrossRefPubMedGoogle Scholar
  37. Steimer T, Driscoll P (2003) Divergent stress responses and coping styles in psychogenetically selected Roman high- (RHA) and low- (RLA) avoidance rats: behavioural, neuroendocrine and developmental aspects. Stress 6:87–100CrossRefPubMedGoogle Scholar
  38. Steimer T, Escorihuela RM, Fernández-Teruel A, Driscoll P (1998) Long-term behavioral and neuroendocrine changes in Roman high- (RHA/Verh) and Low-(RLA/Verh) avoidance rats following neonatal handling. Int J Dev Neurosci 16:165–174CrossRefPubMedGoogle Scholar
  39. Zhang TY, Labonté B, Wen XL, Turecki G, Meaney MJ (2013) Epigenetic Mechanism for the Early Environmental Regulation of Hippocampal Glucocorticoid Receptor Gene Expression in Rodents and Humans. Neuropsychopharmacology 38:111–123CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Cristóbal Río-Álamos
    • 1
  • Cristina Gerbolés
    • 1
  • Carles Tapias-Espinosa
    • 1
  • Daniel Sampedro-Viana
    • 1
  • Ignasi Oliveras
    • 1
  • Ana Sánchez-González
    • 1
  • Toni Cañete
    • 1
  • Gloria Blázquez
    • 1
  • María del Mar López
    • 2
  • Carlos Baldellou
    • 2
  • Pedro J. Otaegui
    • 2
  • Adolf Tobeña
    • 1
  • Alberto Fernández-Teruel
    • 1
  1. 1.Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, School of MedicineUniversitat Autònoma de BarcelonaBellaterraSpain
  2. 2.Servei d’EstabulariUniversitat Autònoma de BarcelonaBellaterraSpain

Personalised recommendations