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Genetic Rat Models of Schizophrenia-Relevant Symptoms

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DOI: 10.4236/wjns.2014.43030    2,933 Downloads   3,831 Views   Citations

ABSTRACT

It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing “normal” genetic, neurobiological and phenotype variation, thus allowing the study of associations among them by means of genetic mapping or gene expression studies.

 

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Río, C. , Oliveras, I. , Cañete, T. , Blázquez, G. , Tobeña, A. and Fernández-Teruel, A. (2014) Genetic Rat Models of Schizophrenia-Relevant Symptoms. World Journal of Neuroscience, 4, 261-278. doi: 10.4236/wjns.2014.43030.

References

[1] Sawa, A. and Snyder, S. (2002) Schizophrenia: Diverse Approaches to a Complex Disease. Science, 296, 692-695.
http://dx.doi.org/10.1126/science.1070532
[2] Powell, C.M. and Miyakawa, T. (2006) Schizophrenia-Relevant Behavioral Testing in Rodent Models: A Uniquely Human Disorder? Biological Psychiatry, 59, 1198-207.
http://dx.doi.org/10.1016/j.biopsych.2006.05.008
[3] Jones, C.A., Watson, D.J.G. and Fone, K.C.F. (2011) Animal Models of Schizophrenia. British Journal of Pharmacology, 164, 1162-1194. http://dx.doi.org/10.1111/j.1476-5381.2011.01386.x
[4] Kapur, S. (2003) Psychosis as a State of Aberrant Salience: A Framework Linking Biology, Phenomenology, and Pharmacology in Schizophrenia. The American Journal of Psychiatry, 160, 13-23.
http://dx.doi.org/10.1176/appi.ajp.160.1.13
[5] Gonzalez-Maeso, J., Ang, R., Yuen, T., Chan, P., Weisstaub, N.V., Lopez-Gimenez, J.F., et al. (2008) Identification of a Serotonin/Glutamate Receptor Complex Implicated in Psychosis. Nature, 452, 93-97.
http://dx.doi.org/10.1038/nature06612
[6] Snyder, S.H. (2008) A Complex in Psychosis. Nature, 452, 38-39. http://dx.doi.org/10.1038/452038a
[7] Gonzalez-Maeso, J. and Sealfon, S.C. (2009) Psychedelics and Schizophrenia. Trends in Neurosciences, 32, 225-232.
http://dx.doi.org/10.1016/j.tins.2008.12.005
[8] Patil, S.T., Zhang, L., Martenyi, F., Lowe, S.L., Jackson, K.A., Andreev, B.V., et al. (2007) Activation of mGlu2/3 Receptors as a New Approach to Treat Schizophrenia: A Randomized Phase 2 Clinical Trial. Nature Medicine, 13, 1102-1107. http://dx.doi.org/10.1038/nm1632
[9] Geyer, M.A., Olivier, B., Joels, M. and Kahn, RS. (2012) From Antipsychotic to Anti-Schizophrenia Drugs: Role of Animal Models. Trends in Pharmacological Sciences, 33, 515-521.
http://dx.doi.org/10.1016/j.tips.2012.06.006
[10] Fernando, A.B. and Robbins, T.W. (2011) Animal Models of Neuropsychiatric Disorders. Annual Reviews of Clinical Psychology, 7, 39-61. http://dx.doi.org/10.1146/annurev-clinpsy-032210-104454
[11] Morris, R. (1984) Developments of a Water-Maze Procedure for Studying Spatial Learning in the Rat. Journal of Neuroscience Methods, 11, 47-60. http://dx.doi.org/10.1016/0165-0270(84)90007-4
[12] Steele, R.J. and Morris, R.G. (1999) Delay-Dependent Impairment of a Matching-to-Place Task with Chronic and Intrahippocampal Infusion of the NMDA-Antagonist D-AP5. Hippocampus, 9, 118-136.
http://dx.doi.org/10.1002/(SICI)1098-1063(1999)9:2<118::AID-HIPO4>3.0.CO;2-8
[13] Moreno, J.L. and González-Maeso, J. (2013) Preclinical Models of Antipsychotic Drug Action. The International Journal of Neuropsychopharmacology, 16, 2131-2144.
http://dx.doi.org/10.1017/S1461145713000606
[14] Swerdlow, N.R., Geyer, M. and Braff, D. (2001) Neural Circuit Regulation of Prepulse Inhibition of Startle in the Rat: Current knowledge and future challenges. Psychopharmacology, 156, 194-215.
http://dx.doi.org/10.1007/s002130100799
[15] Braff, D.L. and Geyer, M.A. (1990). Sensorimotor Gating and Schizophrenia: Human and Animal Model Studies. Archive of General Psychiatry, 47, 181-188.
http://dx.doi.org/10.1001/archpsyc.1990.01810140081011
[16] Geyer, M.A. and Swerdlow, N.R. (2001) Measurement of Startle Response, Prepulse Inhibition and Habituation. Current Protocols in Neuroscience, 3, 8.7.1-8.7.15.
[17] Powell, S.B., Weber, M. and Geyer, M. (2012) Genetic Models of Sensorimotor Gating: Relevance to Neuropsychiatric Disorders. Current Topics in Behavioral Neuroscience, 12, 251-318. http://dx.doi.org/10.1007/7854_2011_195
[18] Ellenbroek, B.A., Geyer, M.A. and Cools, A.R. (1995) The Behavior of APO-SUS Rats in Animal Models with Construct Validity for Schizophrenia. Journal of Neuroscience, 15, 7604-7611.
[19] Shalev, U., Feldon, J. and Weiner, I. (1998) Genderand Age-Dependent Differences in Latent Inhibition Following Pre-Weaning Non-Handling: Implications for a Neurodevelopmental Animal Model of Schizophrenia. International Journal of Developmental Neuroscience, 16, 279-288. http://dx.doi.org/10.1016/S0736-5748(98)00031-8
[20] Fernández-Teruel, A., Blázquez, G., Pérez, M., Aguilar, R., Canete, T., Guitart-Masip, M., et al. (2006) Latent Inhibition Threshold in Roman High-Avoidance Rats: A Psychogenetic Model of Abnormalities in Attentional Filter? Actas Espanolas de Psiquiatría, 34, 257-263.
[21] Palmer, A.A. and Printz, M.P. (1999) Strain Differences in Fos Expression Following Airpuff Startle in Spontaneously Hypertensive and Wistar Kyoto Rats. Neuroscience, 89, 965-978.
http://dx.doi.org/10.1016/S0306-4522(98)00333-9
[22] Swerdlow, N.R., Martinez, Z.A., Hanlon, F.M., Platten, A., Farid, M., Auerbach, P., Braff, D.L. and Geyer, M.A. (2000) Towards Understanding the Biology of a Complex Phenotype: Rat Strain and Substrain Differences in the Sensorimotor Gating-Disruptive Effects of Dopamine Agonists. The Journal of Neuroscience, 20, 4325-4336.
[23] Swerdlow, N.R., Shoemaker, J.M., Platten, A., Pitcher, L., Goins, J. and Crain, S. (2003) Heritable Differences in the Effects of Amphetamine but Not DOI on Startle Gating in Albino and Hooded Outbred Rat Strains. Pharmacology Biochemistry and Behavior, 75, 191-197.
http://dx.doi.org/10.1016/S0091-3057(03)00078-9
[24] Swerdlow, N.R., Shoemaker, J.M., Platten, A., Pitcher, L., Goins, J. and Auerbach, P.P. (2004) Heritable Differences in the Dopaminergic Regulation of Sensorimotor Gating. I. Apomorphine Effects on Startle Gating in Albino and Hooded Outbred Rat Strains and their F1 and N2 Progeny. Psychopharmacology, 174, 441-451.
http://dx.doi.org/10.1007/s00213-003-1481-3
[25] Swerdlow, N.R., Varty, G.B. and Geyer, M.A. (1998) Discrepant Findings of Clozapine Effects on Prepulse Inhibition of Startle: Is It the Route or the Rat? Neuropsychopharmacology, 18, 50-56.
http://dx.doi.org/10.1016/S0893-133X(97)00110-3
[26] Swerdlow, N.R., Platten, A., Kim, Y.K., Gaudet, I., Shoemaker, J., Pitcher, L. and Auerbach, P. (2001) Sensitivity to the Dopaminergic Regulation of Prepulse Inhibition in Rats: Evidence for Genetic, but Not Environmental Determinants. Pharmacology, Biochemistry and Behavior, 70, 219-226. http://dx.doi.org/10.1016/S0091-3057(01)00598-6
[27] Swerdlow,N.R., Platten, A., Hanlon, F.M., Martinez, Z.A., Printz, M.P. and Auerbach, P. (2003) Sensitivity to Sensorimotor Gating-Disruptive Effects of Apomorphine in Two Outbred Parental Rat Strains and their F1 and N2 Progeny. Neuropsychopharmacology, 28, 226-234.
http://dx.doi.org/10.1038/sj.npp.1300035
[28] Swerdlow, N.R., Shilling, P.D., Breier, M., Trim, R.S., Light, G.A. and Saint Marie, R.L. (2012) Fronto-TemporalMesolimbic Gene Expression and Heritable Differences in Amphetamine-Disrupted Sensorimotor Gating in Rats. Psychopharmacology, 224, 349-362. http://dx.doi.org/10.1007/s00213-012-2758-1
[29] Overstreet, D.H., Moy, S.S., Lubin, D.A., Gause, L.R., Lieberman, J.A. and Johns, J.M. (2000) Enduring Effects of Prenatal Cocaine Administration on Emotional Behavior in Rats. Physiology & Behavior, 70, 149-156.
http://dx.doi.org/10.1016/S0031-9384(00)00245-6
[30] Vaillancourt, C. and Boksa, P. (2000) Birth Insult Alters Dopamine-Mediated Behavior in a Precocial Species, the Guinea Pig: Implications for Schizophrenia. Neuropsychopharmacology, 23, 654-666.
http://dx.doi.org/10.1016/S0893-133X(00)00164-0
[31] Sontag, T.A., Cools, A.R. and Ellenbroek, B.A. (2003) Removal of Short-Term Isolation Stress Differentially Influences Prepulse Inhibition in APO-SUS and APO-UNSUS Rats. Behavioural Brain Research, 141, 171-175.
http://dx.doi.org/10.1016/S0166-4328(02)00364-9
[32] Aguilar, R., Gil, L., Tobena, A., Escorihuela, R.M. and Fernández-Teruel, A. (2000) Differential Effects of Cohort Removal Stress on the Acoustic Startle Response of the Roman/Verh Rat Strains. Behavior Genetics, 30, 71-75.
http://dx.doi.org/10.1023/A:1002042711672
[33] Birkett, S.D. and Pickering, B.T. (1988) The Vasopressin Precursor in the Brattleboro (di/di) Rat. International Journal of Peptide and Protein Research, 32, 565-572.
http://dx.doi.org/10.1111/j.1399-3011.1988.tb01388.x
[34] Feifel, D. and Priebe, K. (2001) Vasopressin-Deficient Rats Exhibit Sensorimotor Gating Deficits that Are Reversed by Subchronic Haloperidol. Biological Psychiatry, 50, 425-433.
http://dx.doi.org/10.1016/S0006-3223(01)01100-3
[35] Feifel, D., Mexal, S., Melendez, G., Liu, P.Y., Goldenberg, J.R. and Shilling, P.D. (2009) The Brattleboro Rat Displays a Natural Deficit in Social Discrimination That Is Restored by Clozapine and a Neurotensin Analog. Neuropsychopharmacology, 34, 2011-2018. http://dx.doi.org/10.1038/npp.2009.15
[36] Feifel, D., Shilling, P.D. and Melendez, G. (2011) Further Characterization of the Predictive Validity of the Brattleboro Rat Model for Antipsychotic Efficacy. Journal of Psychopharmacology, 25, 836-841.
http://dx.doi.org/10.1177/0269881110388327
[37] Feifel, D. and Priebe, K. (2007) The Effects of Cross-Fostering on Inherent Sensorimotor Gating Deficits Exhibited by Brattleboro Rats. The Journal of General Psychology, 134, 173-182. http://dx.doi.org/10.3200/GENP.134.2.172-182
[38] Berquist, M.D., Mooney-Leber, S.M., Feifel, D. and Prus, A.J. (2013) Assessment of Attention in Male and Female Brattleboro Rats Using a Self-Paced Five-Choice Serial Reaction Time Task. Brain Research, 1537, 174-179.
http://dx.doi.org/10.1016/j.brainres.2013.09.012
[39] Cilia, J., Gartlon, J.E., Shilliam, C., Dawson, L.A., Moore, S.H. and Jones, D.N. (2010) Further Neurochemical and Behavioural Investigation of Brattleboro Rats as a Putative Model of Schizophrenia. Journal of Psychopharmacology, 24, 407-419.
http://dx.doi.org/10.1177/0269881108098787
[40] Brito, G.N., Thomas, G.J., Gash, D.M. and Kitchen, J.H. (1982) The Behavior of Brattleboro Rats. Annals of the New York Academy of Sciences, 394, 740-748.
http://dx.doi.org/10.1111/j.1749-6632.1982.tb37492.x
[41] Laycock, J.F., Gartside, I.B. and Chapman, J.T. (1983) A Comparison of the Learning Abilities of Brattleboro Rats with Hereditary Diabetes Insipidus and Long-Evans Rats Using Positively Reinforced Operant Conditioning. Progress in Brain Research, 60, 183-187. http://dx.doi.org/10.1016/S0079-6123(08)64385-X
[42] Shilling, P.D., Kinkead, B., Murray, T., Melendez, G., Nemeroff, C.B. and Feifel, D. (2006) Upregulation of Striatal Dopamine-2 Receptors in Brattleboro Rats with Prepulse Inhibition Deficits. Biological Psychiatry, 60, 1278-1281.
http://dx.doi.org/10.1016/j.biopsych.2006.03.045
[43] Sagvolden, T., Metzger, M.A., Schiorbeck, H.K., Rugland, A.L., Spinnangr, I. and Sagvolden, G. (1992) The Spontaneously Hypertensive Rat (SHR) as an Animal Model of Childhood Hyperactivity (ADHD): Changed Reactivity to Reinforcers and to Psychomotor Stimulants. Behavioral and Neural Biology, 58, 103-112.
http://dx.doi.org/10.1016/0163-1047(92)90315-U
[44] Russel, V.A. (2007) Neurobiology of Animal Models of Attention-Deficit Hyperactivity Disorder. Journal of Neuroscience Methods, 166, 1-14. http://dx.doi.org/10.1016/j.jneumeth.2006.12.020
[45] Calzavara, M.B., Levin, R., Medrano, W.A., Almeida, V., Sampaio, A.P., Barone, L.C., et al. (2011) Effects of Antipsychotics and Amphetamine on Social Behaviors in Spontaneously Hypertensive Rats. Behavioural Brain Research, 225, 15-22. http://dx.doi.org/10.1016/j.bbr.2011.06.026
[46] Calzavara, M.B., Medrano, W.A., Levin, R., Kameda, S.R., Andersen, M.L., Tufik, S., et al. (2009) Neuroleptic Drugs Revert the Contextual Fear Conditioning Deficit Presented by Spontaneously Hypertensive Rats: A Potential Animal Model of Emotional Context Processing in Schizophrenia? Schizophrenia Bulletin, 35, 748-759.
http://dx.doi.org/10.1093/schbul/sbn006
[47] Ferguson, S.A. and Cada, A.M. (2004) Spatial Learning/Memory and Social and Nonsocial Behaviors in the Sponta- neously Hypertensive, Wistar-Kyoto and Sprague-Dawley Rat Strains. Pharmacology Biochemistry and Behavior, 77, 583-594. http://dx.doi.org/10.1016/j.pbb.2003.12.014
[48] Levin, R., Peres, F.F., Almeida, V., Calzavara, M.B., Zuardi, A.W., Hallak, J.E., et al. (2014) Effects of Cannabinoid Drugs on the Deficit of Prepulse Inhibition of Startle in an Animal Model of Schizophrenia: The SHR Strain. Frontiers in Pharmacology, 5, 10.
http://dx.doi.org/10.3389/fphar.2014.00010
[49] van den Buuse, M. (2004) Prepulse Inhibition of Acoustic Startle in Spontaneously Hypertensive Rats. Behavioural Brain Research, 154, 331-337. http://dx.doi.org/10.1016/j.bbr.2004.02.021
[50] Lipska, B.K. and Weinberger, D.R. (2000) To Model a Psychiatric Disorder in Animals: Schizophrenia as a Reality Test. Neuropsychopharmacology, 23, 223-239.
http://dx.doi.org/10.1016/S0893-133X(00)00137-8
[51] Sams-Dodd, F. (1998) A Test of the Predictive Validity of Animal Models of Schizophrenia Based on Phencyclidine and D-Amphetamine. Neuropsychopharmacology, 18, 293-304.
http://dx.doi.org/10.1016/S0893-133X(97)00161-9
[52] Freudenberg, F., Dieckmann, M., Winter, S., Koch, M. and Schwabe, K. (2007) Selective Breeding for Deficient Sensorimotor Gating Is Accompanied by Increased Perseveration in Rats. Neuroscience, 148, 612-622.
http://dx.doi.org/10.1016/j.neuroscience.2007.06.034
[53] Schwabe, K., Freudenberg, F. and Koch, M. (2007) Selective Breeding of Reduced Sensorimotor Gating in Wistar Rats. Behavior Genetics, 37, 706-712. http://dx.doi.org/10.1007/s10519-007-9166-z
[54] Cook, D. and Kesner, R.P. (1998) Caudate Nucleus and Memory for Egocentric Localization. Behavioral and Neural Biology, 49, 332-343. http://dx.doi.org/10.1016/S0163-1047(88)90338-X
[55] Kesner, R.P., Bolland, B.L. and Dakis, M. (1993) Memory for Spatial Locations, Motor Responses, and Objects: Triple Dissociations among the Hippocampus, Caudate Nucleus, and Extrastriate Visual Cortex. Experimental Brain Research, 93, 462-470. http://dx.doi.org/10.1007/BF00229361
[56] Hanlon, F.M. and Sutherland, R.J. (2000) Changes in Adult Brain and Behavior Caused by Neonatal Limbic Damage: Implications for the Etiology of Schizophrenia. Behavioural Brain Research, 107, 71-83.
http://dx.doi.org/10.1016/S0166-4328(99)00114-X
[57] Chang, Q. and Gold, P.E. (2003) Intra-Hippocampal Lidocaine Injections Impair Acquisition of a Place Task and Facilitate Acquisition of a Response Task in Rats. Behavioural Brain Research, 144, 19-24.
http://dx.doi.org/10.1016/S0166-4328(03)00063-9
[58] Lysaker, P.H., Bell, M.D., Bryson, G. and Kaplan, E. (1998) Neurocognitive Function and Insight in Schizophrenia: Support for an Association with Impairments in Executive Function. Acta Psychiatrica Scandinavica, 97, 297-301.
http://dx.doi.org/10.1111/j.1600-0447.1998.tb10003.x
[59] Perry, W. and Braff, D.L. (1998) A Multimethod Approach to Assessing Perseverations in Schizophrenia Patients. Schizophrenia Research, 33, 69-77. http://dx.doi.org/10.1016/S0920-9964(98)00061-9
[60] Dieckmann, M., Freudenberg, F., Klein, S., Koch, M. and Schwabe, K. (2007) Disturbed Social Behaviour and Motivation in Rats Selectively Bred for Deficient Sensorimotor Gating. Schizophrenia Research, 97, 250-253.
http://dx.doi.org/10.1016/j.schres.2007.08.007
[61] Hadamitzky, M., Harich, S., Koch, M. and Schwabe, K. (2007) Deficient Prepulse Inhibition Induced by Selective Breeding of Rats Can Be Restored by the Dopamine D2 Antagonist Haloperidol. Behavioural Brain Research, 177, 364-367. http://dx.doi.org/10.1016/j.bbr.2006.11.037
[62] Rhein, M., Muschler, M.R., Krauss, J.K., Bleich, S., Frieling, H. and Schwabe, K. (2013) Hypomethylation of Neuregulin in Rats Selectively Bred for Reduced Sensorimotor Gating. Schizophrenia Research, 150, 262-265.
http://dx.doi.org/10.1016/j.schres.2013.07.012
[63] Weickert, C.S., Tiwari, Y., Schofield, P.R., Mowry, B.J. and Fullerton, J.M. (2012) Schizophrenia-Associated HapICE Haplotype Is Associated with Increased NRG1 Type III Expression and High Nucleotide Diversity. Translational Psychiatry, 2, e104. http://dx.doi.org/10.1038/tp.2012.25
[64] Petrovszki, Z., Adam, G., Tuboly, G., Kekesi, G., Benedek, G., Keri, S., et al. (2013) Characterization of Gene-Environment Interactions by Behavioral Profiling of Selectively Bred Rats: The Effect of NMDA Receptor Inhibition and Social Isolation. Behavioural Brain Research, 240, 134-145. http://dx.doi.org/10.1016/j.bbr.2012.11.022
[65] Cools, A.R., Brachten, R., Heeren, D., Willemen, A. and Ellenbroek, B. (1990) Search after Neurobiological Profile of Individual-Specific Features of Wistar Rats. Brain Research Bulletin, 18, 663-669.
[66] Ellenbroek, B.A., Geyer, M.A. and Cools, A.R. (1995) The Behavior of APO-SUS Rats in Animal Models with Construct Validity for Schizophrenia. Journal of Neuroscience, 15, 7604-7611.
[67] Ellenbroek, B.A. and Cools, A. (2002) Apomorphine Susceptibility and Animal Models for Psycopathology: Genes and Environment. Behavior Genetics, 32, 349-361. http://dx.doi.org/10.1023/A:1020214322065
[68] Cabib, S., Oliverio, A., Ventura, R., Luchesse, F. and Puglisi, A. (1997) Brain Dopamine Receptor Plasticity: Testing a Diathesis-Stress Hypothesis in an Animal Model. Psychopharmacology, 132, 153-160.
http://dx.doi.org/10.1007/s002130050331
[69] Ellenbroek, B.A., Sluyter, F. and Cools, A. (2000) The Role of Genetic and Early Environmental Factors in Determining Apomorphine Susceptibility. Psychopharmacology, 148, 124-131. http://dx.doi.org/10.1007/s002130050033
[70] Cools, A.R., Ellenbroek, B.A., Gingras, M.A., Engbersen, A. and Heeren, D. (1997) Differences in Vulnerability and Susceptibility to Dexamphetamine in Nijmegen High and Low Responders to Novelty: A Dose-Effect Analysis of SpatioTemporal Programming of Behaviour. Psychopharmacology, 132, 181-187.
http://dx.doi.org/10.1007/s002130050334
[71] Van der Elst, M.C., Ellenbroek, B.A. and Cools, A.R. (2006) Cocaine Strongly Reduces Prepulse Inhibition in Apomorphine-Susceptible Rats, but Not in Apomorphine-Unsusceptible Rats: Regulation by Dopamine D2 Receptors. Be- havioural Brain Research, 175, 392-398.
http://dx.doi.org/10.1016/j.bbr.2006.09.014
[72] Aguilar, R., Gil, L., Fernández-Teruel, A. and Tobena, A. (2000) Genetically-Based Behavioral Traits Influence the Effects of Shuttle Box Avoidance Overtraining and Extinction upon Intertrial Responding: A Study with the Roman Rat Strains. Behavioural Processes, 66, 63-72.
http://dx.doi.org/10.1016/j.beproc.2004.01.002
[73] Bignami, G. (1965) Selection for High Rates and Low Rates of Avoidance Conditioning in the Rat. Animal Behaviour, 13, 221-227. http://dx.doi.org/10.1016/0003-3472(65)90038-2
[74] Driscoll, P. and Bttig, 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, Elsevier, Amsterdam, 95-123.
[75] Driscoll, P., Escorihuela, R.M., Fernández-Teruel, A., Giorgi, O., Schwegler, H., Steimer, T.H., et al. (1998) Genetic Selection and Differential Stress Responses: The Roman Lines/Strain of Rats. Annals of the New York Academy of Sciences, 851, 501-510.
[76] Driscoll, P., Fernández-Teruel, A., Corda, M.G., Giorgi, O. and Steimer, T. (2009) Some Guidelines for Defining Personality Differences in Rats. In: Yong-Kyu, K., Ed., Handbook of Behavior Genetics, Springer, New York, 281-300.
http://dx.doi.org/10.1007/978-0-387-76727-7_20
[77] Escorihuela, R.M., Tobena, A., Driscoll, P. and Fernández-Teruel, A. (1995) Effects of Training, Early Handling, and Perinatal Flumazenil on Shuttle Box Acquisition in Roman Low-Avoidance Rats: Toward Overcoming a Genetic Deficit. Neuroscience & Biobehavioral Reviews, 19, 353-367. http://dx.doi.org/10.1016/0149-7634(94)00051-2
[78] Escorihuela, R.M., Fernández-Teruel, A., Gil, L., Aguilar, R., Tobena, A. and Driscoll, P. (1999) Inbred Roman Highand Low-Avoidance Rats Differences in Anxiety, Novelty Seeking, and Shuttlebox Behaviors. Physiology & Behavior, 67, 19-26. http://dx.doi.org/10.1016/S0031-9384(99)00064-5
[79] Fernandez-Teruel, A., Escorihuela, R.M., Castellano, B., Gonzalez, B. and Tobena, A. (1997) Neonatal Handling and Environmental Enrichment Effects on Emotionality, Novelty/Reward Seeking, and Age-Related Cognitive and Hippocampal Impairments: Focus on the Roman Rat Lines. Behavior Genetics, 27, 513-526.
http://dx.doi.org/10.1023/A:1021400830503
[80] López-Aumatell, R., Vicens-Costa, E., Guitart-Masip, M., Martínez-Membrives, E., Valdar, W., Johannesson, M., et al. (2009) Unlearned Anxiety Predicts Learned Fear: A Comparison among Heterogeneous Rats and the Roman Rat Strains. Behavioural Brain Research, 202, 92-101. http://dx.doi.org/10.1016/j.bbr.2009.03.024
[81] López-Aumatell, R., Vicens-Costa, E., Guitart-Masip, M., Martínez-Membrives, E., Valdar, W., Johannesson, M., et al. (2009) Ansiedad en Ratas Genéticamente Heterogéneas: Hacia la Identificación de Genes para Caracteres Conductuales Cuantitativos. Ansiedad y Estrés, 15, 67-84.
[82] Diaz-Moran, S., Palència, M., Mont-Cardona, C., Canete, T., Blázquez, G., Martínez-Membrives, E., et al. (2012) Coping Style and Stress Hormone Responses in Genetically Heterogeneous Rats: Comparison with the Roman Rat Strains. Behavioural Brain Research, 228, 203-210. http://dx.doi.org/10.1016/j.bbr.2011.12.002
[83] Díaz-Morán, S., Martínez-Membrives, E., López-Aumatell, R., Canete, T., Blázquez, G., Palencia, M., et al. (2013) What Can We Learn on Rodent Fearfulness/Anxiety from the Genetically Heterogeneous NIH-HS Rat Stock? Open Journal of Psychiatry, 3, 238-250. http://dx.doi.org/10.4236/ojpsych.2013.32022
[84] Estanislau, C., Díaz-Morán, S., Canete, T., Blázquez, G., Tobena, A. and Fernández-Teruel, A. (2013) Context-Dependent Differences in Grooming Behavior among the NIH Heterogeneous Stock and the Roman Highand LowAvoidance Rats. Neuroscience Research, 77, 187-201. http://dx.doi.org/10.1016/j.neures.2013.09.012
[85] Carrasco, J., Márquez, C., Nadal, R., Tobena, A., Fernández-Teruel, A. and Armario, A. (2008) Characterization of Central and Peripheral Components of the Hypothalamus-Pituitary-Adrenal Axis in the Inbred Roman Rat Strains. Psychoneuroendocrinology, 33, 437-445. http://dx.doi.org/10.1016/j.psyneuen.2008.01.001
[86] Steimer, T. and 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, 87-100. http://dx.doi.org/10.1080/1025389031000111320
[87] Steimer, T. and Driscoll, P. (2005) Inter-Individual vs Line/Strain Differences in Psychogenetically Selected Roman High-(RHA) and Low-(RLA) Avoidance Rats: Neuroendocrine and Behavioural Aspects. Neuroscience & Biobehavioral Reviews, 29, 99-112.
http://dx.doi.org/10.1016/j.neubiorev.2004.07.002
[88] Schwegler, H., Pilz, P.K.D., Koch, M., Fendt, M., Linke, R. and Driscoll, P. (1997) The Acoustic Startle Response in Inbred Roman Highand Low-Avoidance Rats. Behavior Genetics, 27, 579-581.
[89] Fernandez-Teruel, A., Escorihuela, R.M., Driscoll, P., Tobena, A. and Bttig, K. (1991) Infantile (Handling) Stimulation and Behavior in Young Roman High- and Low-Avoidance Rats. Physiology & Behavior, 50, 563-565.
http://dx.doi.org/10.1016/0031-9384(91)90546-Z
[90] Fernandez-Teruel, A., Escorihuela, R.M., Nuez, J.F., Gomá, M., Driscoll, P. and Tobena, A. (1992) Early Stimulation Effects on Novelty-Induced Behavior in Two Psychogenetically-Selected Rat Lines with Divergent Emotionality Pro- files. Neuroscience Letters, 137, 185-188.
http://dx.doi.org/10.1016/0304-3940(92)90400-2
[91] Ferré, P., Fernández-Teruel, A., Escorihuela, R.M., Driscoll, P., Corda, M.G., Giorgi, O., et al. (1995) Behavior of the Roman/Verh High- and Low-Avoidance Rat Lines in Anxiety Tests: Relationship with Defecation and Self-Grooming. Physiology & Behavior, 58, 1209-1213.
http://dx.doi.org/10.1016/0031-9384(95)02068-3
[92] López-Aumatell, R., Blázquez, G., Gil, L., Aguilar, R., Canete, T., Giménez-Llort, L., et al. (2009) The Roman High- and Low-Avoidance Rat Strains Differ in Fear-Potentiated Startle and Classical Aversive Conditioning. Psicothema, 21, 27-32.
[93] Yilmazer-Hanke, D.M., Faber-Zuschratter, H., Linke, R. and Schwegler, H. (2002) Contribution of Amygdala Neurons Containing Peptides and Calcium-Binding Proteins to Fear-Potentiated Startle and Exploration-Related Anxiety in Inbred Roman High- and Low-Avoidance Rats. European Journal of Neuroscience, 15, 1206-1218.
http://dx.doi.org/10.1046/j.1460-9568.2002.01945.x
[94] Manzo, L., Gómez, M.J., Callejas-Aguilera, J.E., Fernández-Teruel, A., Papini, M.R. and Torres, C. (2014) AntiAnxiety Self-Medication Induced by Incentive Loss in Rats. Physiology & Behavior, 123, 86-92.
http://dx.doi.org/10.1016/j.physbeh.2013.10.002
[95] Corda, M.G., Lecca, D., Piras, G., Di Chiara, G. and Giorgi, O. (1997) Biochemical Parameters of Dopaminergic and Gabaergic Neurotransmission in the CNS of Roman High-Avoidance and Roman Low-Avoidance Rats. Behavior Genetics, 27, 527-536. http://dx.doi.org/10.1023/A:1021452814574
[96] Escorihuela, R.M., Tobena, A. and Fernandez-Teruel, A. (1995) Environmental Enrichment and Postnatal Handling Prevent Spatial Learning Deficits in Aged Hypoemotional (Roman High-Avoidance) and Hyperemotional (Roman Low-Avoidance) Rats. Learning and Memory, 2, 40-48.
http://dx.doi.org/10.1101/lm.2.1.40
[97] Escorihuela, R.M., Fernández-Teruel, A., Tobena, A., Langhans, W., Bttig, K. and Driscoll, P. (1997) Labyrinth Exploration, Emotional Reactivity, and Conditioned Fear in Young Roman/Verh Inbred Rats. Behavior Genetics, 27, 573-578. http://dx.doi.org/10.1023/A:1021413200461?
[98] Aguilar, R., Escorihuela, R.M., Gil, L., Tobena, A. and Fernández-Teruel, A. (2002) Differences between Two Psychogenetically Selected Lines of Rats in a Swimming Pool Matching-to-Place Task: Long-Term Effects of Infantile Stimulation. Behavior Genetics, 32, 127-134. http://dx.doi.org/10.1023/A:1015253807488
[99] Moreno, M., Cardona, D., Gómez, M.J., Sánchez-Santed, F., Tobena, A., Fernández-Teruel, A., et al. (2010) Impulsivity Characterization in the Roman High- and Low-Avoidance Rat Strains: Behavioral and Neurochemical Differences. Neuropsychopharmacology, 35, 1198-1208.
http://dx.doi.org/10.1038/npp.2009.224
[100] Driscoll, P., Ferré, P., Fernández-Teruel, A., Levi de Stein, M., Wolfman, C., Medina, J., et al. (1995) Effects of Prenatal Diazepam on Two-Way Avoidance Behavior, Swimming Navigation and Brain Levels of Benzodiazepine-Like Molecules in Male Roman High- and Low-Avoidance Rats. Psychopharmacology, 122, 51-57.
http://dx.doi.org/10.1007/BF02246441
[101] Nil, R. and Bttig, K. (1981) Spontaneous Maze Ambulation and Hebb-Williams Learning in Roman High-Avoidance and Roman Low-Avoidance Rats. Behavioral and Neural Biology, 33, 465-475.
http://dx.doi.org/10.1016/S0163-1047(81)91833-1
[102] Manzo, L., Gómez, M.J., Callejas-Aguilera, J.E., Donaire, R., Sabariego, M., Fernández-Teruel, A., et al. (2014) Relationship between Ethanol Preference and Sensation/Novelty Seeking. Physiology & Behavior, 133, 53-60.
http://dx.doi.org/10.1016/j.physbeh.2014.05.003
[103] Zeier, H., Baettig, K. and Driscoll, P. (1978) Acquisition of DRL-20 Behavior in Male and Female, Roman High- and Low-Avoidance Rats. Physiology & Behavior, 20, 791-793.
http://dx.doi.org/10.1016/0031-9384(78)90307-4
[104] Giorgi, O., Piras, G. and Corda, M.G. (2007) The Psychogenetically Selected Roman High- and Low-Avoidance Rat Lines: A Model to Study the Individual Vulnerability to Drug Addiction. Neuroscience & Biobehavioral Reviews, 31, 148-163. http://dx.doi.org/10.1016/j.neubiorev.2006.07.008
[105] Fattore, L., Piras, G., Corda, M.G. and Giorgi, O. (2009) The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration. Neuropsychopharmacology, 34, 1091-1101.
http://dx.doi.org/10.1038/npp.2008.43
[106] Corda, M.G., Piras, G., Lecca, D., Fernández-Teruel, A., Driscoll, P. and Giorgi, O. (2005) The Psychogenetically Selected Roman Rat Lines Differ in the Susceptibility to Develop Amphetamine Sensitization. Behavioural Brain Research, 157, 147-156.
http://dx.doi.org/10.1016/j.bbr.2004.06.016
[107] Giorgi, O., Lecca, D., Piras, G., Driscoll, P. and Corda, M.G. (2003) Dissociation between Mesocortical Dopamine Release and Fear-Related Behaviours in Two Psychogenetically Selected Lines of Rats that Differ in Coping Strategies to Aversive Conditions. European Journal of Neuroscience, 17, 2716-2726.
http://dx.doi.org/10.1046/j.1460-9568.2003.02689.x
[108] Sallés, J., López de Jesús, M., Goi, O., Fernández-Teruel, A., Driscoll, P., Tobena, A., et al. (2001) Transmembrane Signaling through Phospholipase C in Cortical and Hippocampal Membranes of Psychogenetically Selected Rat Lines. Psychopharmacology, 154, 115-125. http://dx.doi.org/10.1007/s002130000621?
[109] Guitart-Masip, M., Johansson, B., Canete, T., Fernández-Teruel, A., Tobena, A., Terenius, L. and Giménez-Llort, L. (2008) Regional Adaptations in PSD-95, NGFI-A and Secretogranin Gene Transcripts Related to Vulnerability to Behavioral Sensitization to Amphetamine in the Roman Rat Strains. Neuroscience, 151, 195-208.
http://dx.doi.org/10.1016/j.neuroscience.2007.09.072
[110] Garcia-Falgueras, A., Castillo-Ruiz, M.M., Put, T., Tobena, A. and Fernández-Teruel, A. (2012) Differential Hippocampal Neuron Density between Inbred Roman High(Low Anxious) and Low-Avoidance (High Anxious) Rats. Neuroscience Letters, 522, 41-46.
http://dx.doi.org/10.1016/j.neulet.2012.06.011
[111] Meyza, K.Z., Boguszewski, P.M., Nikolaev, E. and 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 a Distinct Pattern of Neuronal Activation in the Fear/Anxiety Circuit. Behavior Genetics, 39, 48-61. http://dx.doi.org/10.1007/s10519-008-9234-z
[112] Bentareha, R., Araujo, F., Ruano, D., Driscoll, P., Escorihuela, R.M., Tobena, A., et al. (1998) Pharmacological Properties of the GABA(A) Receptor Complex from Brain Regions of (Hypoemotional) Roman High- and (Hyperemotional) Low-Avoidance Rats. European Journal of Pharmacology, 354, 91-97.
http://dx.doi.org/10.1016/S0014-2999(98)00428-2?
[113] Klein, A.B., Ultved, L., Adamsen, D., Santini, M.A., Tobena, A., Fernandez-Teruel, A., et al. (2014) 5-HT2A 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, 36-45. http://dx.doi.org/10.1016/j.neuroscience.2013.12.063
[114] Giménez-Llort, L., Canete, T., Guitart-Masip, M., Fernández-Teruel, A. and Tobena, A. (2005) Two Distinctive Apomorphine-Induced Phenotypes in the Roman Highand Low-Avoidance Rats. Physiology & Behavior, 86, 458-466.
http://dx.doi.org/10.1016/j.physbeh.2005.07.021?
[115] Coppens, C.M., de Boer, S.F., Steimer, T. and Koolhaas, J.M. (2012) Impulsivity and Aggressive Behavior in Roman High and Low Avoidance Rats: Baseline Differences and Adolescent Social Stress Induced Changes. Physiology & Behavior, 105, 1156-1160.
http://dx.doi.org/10.1016/j.physbeh.2011.12.013
[116] Del Río, C., Oliveras, I., Canete, T., Blázquez, G., Tobena, A. and Fernández-Teruel, A. (2013) Déficits de Filtraje Atencional y en Funciones Ejecutivas en Ratas “Roman de Alta Evitacion” (RHA): Aproximación a un Modelo Animal de Esquizofrenia. Unpublished Master Thesis, Autonomous University of Barcelona, Cerdanyola del Vallès.

  
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