Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-10T17:32:34.519Z Has data issue: false hasContentIssue false
  • English
  • Français

Neurochemical differences in two rat strains exposed to social isolation rearing

Published online by Cambridge University Press:  24 June 2014

Luigia Trabace ,
Margherita Zotti ,
Marilena Colaianna ,
Maria G. Morgese ,
Stefania Schiavone ,
Paolo Tucci ,
Brian H. Harvey ,
Gregers Wegener  and
Vincenzo Cuomo
Luigia Trabace*
Affiliation:
Department of Biomedical Sciences, University of Foggia, Foggia, Italy
Margherita Zotti
Affiliation:
Department of Biomedical Sciences, University of Foggia, Foggia, Italy
Marilena Colaianna
Affiliation:
Department of Biomedical Sciences, University of Foggia, Foggia, Italy
Maria G. Morgese
Affiliation:
Department of Biomedical Sciences, University of Foggia, Foggia, Italy
Stefania Schiavone
Affiliation:
Department of Biomedical Sciences, University of Foggia, Foggia, Italy
Paolo Tucci
Affiliation:
Department of Biomedical Sciences, University of Foggia, Foggia, Italy
Brian H. Harvey
Affiliation:
Unit for Drug Research and Development, Division of Pharmacology, School of Pharmacy, North-West University, Potchefstroom, South Africa
Gregers Wegener
Affiliation:
Centre for Psychiatric Research, University of Aarhus, Aarhus, Denmark
Vincenzo Cuomo
Affiliation:
Department of Human Physiology and Pharmacology, Vittorio Erspamer, University of Rome “La Sapienza”, Rome, Italy
*
Luigia Trabace, PhD, Department of Biomedical Sciences, Faculty of Medicine c/o OO.RR., University of Foggia, Viale L. Pinto, 71100 Foggia, Italy. Tel: +39 0881 588056; Fax: +39 0881 712366; E-mail: trabace@unifg.it
Get access Rights & Permissions [Opens in a new window]

Extract

Objective: Isolation rearing of rats provides a non-pharmacological method of inducing behavioural changes in rodents that resemble schizophrenia or depression. Nevertheless, results are variable within different strains. We focused on neurochemical changes in several in vivo and post-mortem brain regions of Wistar (W) and Lister Hooded (LH) rats following post-weaning social separation.

Methods: Experiments were conducted after 6–8 weeks of isolation. For post-mortem studies, prefrontal cortex (PFC), nucleus accumbens (NAC), hippocampus (Hipp) and striatum (St) were collected by tissue dissection. In vivo experiments were conducted by microdialysis in the PFC. Analyses of dopamine (DA), serotonin (5-HT) levels and relative turnover were performed by using high-performance liquid chromatography.

Results: We found significant strain-related differences in biogenic amine content. LH rats were characterised by markedly raised DA, along with its turnover reduction, in all the post-mortem brain regions examined as well as in microdialysis samples, while in W rats 5-HT tissue concentration was lower in PFC and St and higher in NAC and Hipp. Cortical extracellular 5-HT concentrations were increased in group housed and decreased in isolated W animals. Moreover, isolation increased DA concentrations in the PFC of LH rats, and decreased 5-HT in W rats in NAC and Hipp. Lately, 5-HT turnover was also affected by both strain and isolation conditions.

Conclusions: This study suggests that W and LH rats have markedly different neurochemical profiles in response to isolation, resulting in altered monoamine levels that vary according to brain area and rat strain. These findings highlight the importance of selecting an appropriate rat strain when considering isolation rearing to model symptoms of schizophrenia and/or depression.

Keywords

dopamine and serotoninisolation rearingLister HoodedWistar
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 5 , October 2012 , pp. 286 - 295
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Harvey, BH, Shahid, M.Metabotropic and ionotropic glutamate receptors as neurobiological targets in anxiety and stress-related disorders: focus on pharmacology and preclinical translational models. Pharmacol Biochem Behav 2011. [E-pub ahead of print; DOI: 10.1016/j.pbb.2011.06.014]Google ScholarPubMed
2Yung, AR, Buckby, JA, Cosgrave, EM et al. Association between psychotic experiences and depression in a clinical sample over 6 months. Schizophr Res 2007;91:246–253.CrossRefGoogle Scholar
3Muchimapura, S, Marsden, CA.The effect of social isolation rearing on the development of the hippocampus and serotonergic function. Thai J Physiol Sci 2004;17:1–8.Google Scholar
4Weiss, IC, Feldon, J.Environmental animal models for sensorimotor gating deficiencies in schizophrenia: a review. Psychopharmacology (Berl) 2001;156:305–326.CrossRefGoogle ScholarPubMed
5King, MV, Seeman, P, Marsden, CA, Fone, KC.Increased dopamine D2High receptors in rats reared in social isolation. Synapse 2009;63:476–483.CrossRefGoogle ScholarPubMed
6Geyer, MA, Ellenbroek, B.Animal behavior models of the mechanisms underlying antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:1071–1079.CrossRefGoogle ScholarPubMed
7Lapiz, MD, Fulford, A, Muchimapura, S, Mason, R, Parker, T, Marsden, CA.Influence of postweaning social isolation in the rat on brain development, conditioned behavior, and neurotransmission. Neurosci Behav Physiol 2003;33:13–29.CrossRefGoogle ScholarPubMed
8Geyer, MA, Wilkinson, LS, Humby, T, Robbins, TW.Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. Biol Psychiatry 1993;34:361–372.CrossRefGoogle ScholarPubMed
9Braff, DL, Geyer, MA, Light, GA et al. Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophr Res 2001;49:171–178.CrossRefGoogle ScholarPubMed
10Heim, C, Plotsky, PM, Nemeroff, CB.Importance of studying the contributions of early adverse experience to neurobiological findings in depression. Neuropsychopharmacology 2004;29:641–648.CrossRefGoogle ScholarPubMed
11Fone, KC, Porkess, MV.Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders. Neurosci Biobehav Rev 2008;32:1087–1102.CrossRefGoogle ScholarPubMed
12Cilia, J, Reavill, C, Hagan, JJ, Jones, DN.Long-term evaluation of isolation-rearing induced prepulse inhibition deficits in rats. Psychopharmacology (Berl) 2001;156:327–337.CrossRefGoogle ScholarPubMed
13Lukkes, JL, Watt, MJ, Lowry, CA, Forster, GL.Consequences of post-weaning social isolation on anxiety behavior and related neural circuits in rodents. Front Behav Neurosci 2009;3:18.CrossRefGoogle ScholarPubMed
14Harvey, BH, Stein, DJ, Emsley, RA.The new-generation anti-psychotics: integrating the neuro-pathology and pharmacology of schizophrenia. S Afr Med J 1999;89:661–672.Google Scholar
15Marsden, CA, King, MV, Fone, KC.Influence of social isolation in the rat on serotonergic function and memory–relevance to models of schizophrenia and the role of 5-HT6 receptors. Neuropharmacology 2011;61:400–407.CrossRefGoogle ScholarPubMed
16Shelton, RC, Osuntokun, O, Heinloth, AN, Corya, SA.Therapeutic options for treatment-resistant depression. CNS Drugs 2010;24:131–161.CrossRefGoogle ScholarPubMed
17Ferdman, N, Murmu, RP, Bock, J, Braun, K, Leshem, M.Weaning age, social isolation, and gender, interact to determine adult explorative and social behavior, and dendritic and spine morphology in prefrontal cortex of rats. Behav Brain Res 2007;180:174–182.CrossRefGoogle ScholarPubMed
18Hall, FS, Huang, S, Fong, GW, Sundstrom, JM, Pert, A.Differential basis of strain and rearing effects on open-field behavior in Fawn Hooded and Wistar rats. Physiol Behav 2000;71:525–532.CrossRefGoogle ScholarPubMed
19Ennaceur, A, Michalikova, S, Bradford, A, Ahmed, S.Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks. Behav Brain Res 2005;159:247–266.CrossRefGoogle ScholarPubMed
20Broersen, LM, Uylings, HB.Visual attention task performance in Wistar and Lister hooded rats: response inhibition deficits after medial prefrontal cortex lesions. Neuroscience 1999;94:47–57.CrossRefGoogle ScholarPubMed
21Martins-de-Souza, D, Gattaz, WF, Schmitt, A et al. Proteomic analysis of dorsolateral prefrontal cortex indicates the involvement of cytoskeleton, oligodendrocyte, energy metabolism and new potential markers in schizophrenia. J Psychiatr Res 2009;43:978–986.CrossRefGoogle ScholarPubMed
22Leng, A, Feldon, J, Ferger, B.Long-term social isolation and medial prefrontal cortex: dopaminergic and cholinergic neurotransmission. Pharmacol Biochem Behav 2004;77:371–379.CrossRefGoogle ScholarPubMed
23Lehmann, J, Feldon, J.Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing? Rev Neurosci 2000;11:383–408.CrossRefGoogle ScholarPubMed
24Paxinos, G, Watson, C.The rat brain in stereotaxic coordinates. New York: Elsevier Academic Press, 1998.Google Scholar
25Robinson, TE, Whishaw, IQ.Normalization of extracellular dopamine in striatum following recovery from a partial unilateral 6-OHDA lesion of the substantia nigra: a microdialysis study in freely moving rats. Brain Res 1988;450:209–224.CrossRefGoogle ScholarPubMed
26Trabace, L, Kendrick, KM, Castrignano, S et al. Soluble amyloid beta1-42 reduces dopamine levels in rat prefrontal cortex: relationship to nitric oxide. Neuroscience 2007;147:652–663.CrossRefGoogle ScholarPubMed
27Holmes, PV.Rodent models of depression: reexamining validity without anthropomorphic inference. Crit Rev Neurobiol 2003;15:143–174.CrossRefGoogle ScholarPubMed
28Jentsch, JD, Roth, RH.The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1999;20:201–225.CrossRefGoogle Scholar
29Geyer, MA, Moghaddam, B.Animal model relevant to schizophrenia disorders. In: Davies, KL, Charney, D, Coyle, JT, Nemeroff, C, eds. Neuropsychopharmacology: The Fifth Generation of Progress. Nashville, TN: American College of Neuropsychopharmacology, 2002.Google Scholar
30Swerdlow, NR, Geyer, MA, Braff, DL.Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology (Berl) 2001;156:194–215.CrossRefGoogle ScholarPubMed
31Weiss, IC, Di Iorio, L, Feldon, J, Domeney, AM.Strain differences in the isolation-induced effects on prepulse inhibition of the acoustic startle response and on locomotor activity. Behav Neurosci 2000;114:364–373.CrossRefGoogle ScholarPubMed
32Kinney, GG, Wilkinson, LO, Saywell, KL, Tricklebank, MD.Rat strain differences in the ability to disrupt sensorimotor gating are limited to the dopaminergic system, specific to prepulse inhibition, and unrelated to changes in startle amplitude or nucleus accumbens dopamine receptor sensitivity. J Neurosci 1999;19:5644–5653.CrossRefGoogle ScholarPubMed
33Harvey, BH, Naciti, C, Brand, L, Stein, DJ.Endocrine, cognitive and hippocampal/cortical 5HT 1A/2A receptor changes evoked by a time-dependent sensitisation (TDS) stress model in rats. Brain Res 2003;983:97–107.CrossRefGoogle ScholarPubMed
34Miura, H, Qiao, H, Kitagami, T, Ohta, T, Ozaki, N.Effects of fluvoxamine on levels of dopamine, serotonin, and their metabolites in the hippocampus elicited by isolation housing and novelty stress in adult rats. Int J Neurosci 2005;115:367–378.CrossRefGoogle ScholarPubMed
35El Yacoubi, M, Bouali, S, Popa, D et al. Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression. Proc Natl Acad Sci U S A 2003;100:6227–6232.CrossRefGoogle ScholarPubMed
36Owens, DG, Miller, P, Lawrie, SM, Johnstone, EC.Pathogenesis of schizophrenia: a psychopathological perspective. Br J Psychiatry 2005;186:386–393.CrossRefGoogle ScholarPubMed
37an der Heiden, W, Konnecke, R, Maurer, K, Ropeter, D, Hafner, H.Depression in the long-term course of schizophrenia. Eur Arch Psychiatry Clin Neurosci 2005;255: 174–184.CrossRefGoogle ScholarPubMed
38Brenes, JC, Rodriguez, O, Fornaguera, J.Differential effect of environment enrichment and social isolation on depressive-like behavior, spontaneous activity and serotonin and norepinephrine concentration in prefrontal cortex and ventral striatum. Pharmacol Biochem Behav 2008;89:85–93.Google Scholar
39Brenes, JC, Fornaguera, J.The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum. Behav Brain Res 2009;198:199–205.CrossRefGoogle ScholarPubMed
40Powell, SB, Sejnowski, TJ, Behrens, MM.Behavioral and neurochemical consequences of cortical oxidative stress on parvalbumin-interneuron maturation in rodent models of schizophrenia. Neuropharmacology 2011. [E-pub ahead of print; DOI: 10.1016/j.neuropharm.2011.01.049]Google ScholarPubMed