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Psychopharmacology

, Volume 211, Issue 4, pp 403–414 | Cite as

Effects of antidepressants on the performance in the forced swim test of two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions

  • Giovanna Piras
  • Osvaldo Giorgi
  • Maria G. Corda
original investigation

Abstract

Introduction

The selective breeding of Roman low-avoidance (RLA) and high-avoidance (RHA) rats for, respectively, poor versus rapid acquisition of active avoidance in a shuttle-box has produced two phenotypes that differ drastically in the reactivity to stressful stimuli: in tests used to assess emotionality, RLA rats display passive (“reactive”) coping and robust hypothalamus–pituitary–adrenal (HPA) axis reactivity, whereas RHA rats show proactive coping and blunted HPA axis responses. The behavioral and neuroendocrine traits that distinguish these lines suggest that RLA rats may be prone, whereas RHA rats may be resistant to develop depression-like behavior when exposed to stressful experimental conditions.

Objective and methods

To evaluate the performance of the Roman lines in the forced swim test, immobility, climbing, and swimming were assessed under baseline conditions (i.e., pretest in naïve animals or test after the administration of vehicle), and after subacute treatment with desipramine, fluoxetine, and chlorimipramine.

Results

Under baseline conditions, RLA rats displayed greater immobility and fewer climbing counts than RHA rats. In RLA rats, desipramine, fluoxetine, and chlorimipramine decreased immobility; moreover, desipramine and chlorimipramine increased climbing, whereas fluoxetine increased swimming. In RHA rats, none of these drugs affected immobility, swimming, or climbing.

Conclusions

RLA and RHA rats represent two divergent phenotypes respectively susceptible and resistant to display depression-like behavior in the forced swim test. Hence, comparative studies in these lines may help to develop novel working hypotheses on the relationships among genotype, temperament traits, and neural mechanisms underlying the vulnerability or resistance to stress-induced depression in humans.

Keywords

Roman high- and low-avoidance rats Forced swim test Antidepressants Genetic selection Coping style 

Notes

Acknowledgements

This project was supported by funds from Ministero dell' Università e della Ricerca to M.G.C. and O.G.

References

  1. aan het Rot M, Mathew SJ, Charney DS (2009) Neurobiological mechanisms in major depressive disorder. CMAJ 180:305–313. doi: 10.1503/cmaj.080697 PubMedGoogle Scholar
  2. Aguilar R, Gil L, Flint J, Gray JA, Dawson GR, Driscoll P, Giménez-Llort L, Escorihuela RM, Fernández-Teruel A, Tobeña A (2002) Learned fear, emotional reactivity and fear of heights: a factor analytic map from a large F2 intercross of Roman rat strains. Brain Res Bull 57:17–26. doi: 10.1016/S0361-9230(01)00632-3 CrossRefPubMedGoogle Scholar
  3. Armario A, Gavaldà A, Martí J (1995) Comparison of the behavioural and endocrine response to forced swimming stress in five inbred strains of rats. Psychoneuroendocrinology 20:879–890. doi: 10.1016/0306-4530(95)00018-6 CrossRefPubMedGoogle Scholar
  4. Bignami G (1965) Selection for high rates and low rates of avoidance conditioning in the rat. Anim Behav 13:221–227. doi: 10.1016/0003-3472(65)90038-2 CrossRefPubMedGoogle Scholar
  5. Borsini F, Lecci A, Sessarego A, Frassine R, Meli A (1989) Discovery of antidepressant activity by forced swimming test may depend on pre-exposure of rats to a stressful situation. Psychopharmacology 97:183–188. doi: 10.1007/BF00442247 CrossRefPubMedGoogle Scholar
  6. 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 strains. Psychoneuroendocrinology 33:437–445. doi: 10.1016/j.psyneuen.2008.01.001 CrossRefPubMedGoogle Scholar
  7. Charnay Y, Steimer T, Huguenin C, Driscoll P (1995) [3H] Paroxetine binding sites: brain regional differences between two psychogenetically selected lines of rats. Neurosci Res Comm 16:29–35Google Scholar
  8. Charney DS (2004) Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry 161:195–216CrossRefPubMedGoogle Scholar
  9. Corda MG, Lecca D, Piras G, Di Chiara G, Giorgi O (1997a) Biochemical parameters of dopaminergic and GABAergic neurotransmission in the CNS of Roman high-avoidance and Roman low-avoidance rats. Behav Genet 27:527–536CrossRefPubMedGoogle Scholar
  10. Corda MG, Lecca D, Piras G, Di Chiara G, Giorgi O (1997b) Tail-pinch and pentylenetetrazol increase the release of serotonin in the celebral cortex of Roman high-avoidance, but not low avoidance rats. Neurosci. Meeting Abstract book 23:1850Google Scholar
  11. Crabbe JC, Wahlsten D, Dudek BC (1999) Genetics of mouse behavior: interactions with laboratory environment. Science 284:1670–1672CrossRefPubMedGoogle Scholar
  12. Cryan JF, Page ME, Lucki I (2005a) Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment. Psychopharmacology 182:335–344. doi: 10.1007/s00213-005-0093-5 CrossRefPubMedGoogle Scholar
  13. Cryan JF, Valentino RJ, Lucki I (2005b) Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav Rev 29:547–569. doi: 10.1016/j.neubiorev.2005.03.008 CrossRefPubMedGoogle Scholar
  14. D’Angio M, Serrano A, Driscoll P, Scatton B (1988) Stressful environmental stimuli increase extracellular DOPAC levels in the prefrontal cortex of hypoemotional (Roman high-avoidance) but not hyperemotional (Roman low-avoidance) rats. An in vivo voltammetric study. Brain Res 451:237–247. doi: 10.1016/0006-8993(88)90768-8 CrossRefPubMedGoogle Scholar
  15. De Pablo JM, Parra A, Segovia S, Guillamón A (1989) Learned immobility explains the behavior of rats in the forced swimming test. Physiol Behav 46:229–237. doi: 10.1016/0031-9384(89)90261-8 CrossRefPubMedGoogle Scholar
  16. Detke MJ, Rickels M, Lucki I (1995) Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 121:66–72. doi: 10.1007/BF02245592 CrossRefPubMedGoogle Scholar
  17. Driscoll P, Bättig K (1982) Behavioral, 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, pp 95–123Google Scholar
  18. Driscoll P, Escorihuela RM, Fernández-Teruel A, Giorgi O, Schwegler H, Steimer T, Wiersma A, Corda MG, Flint J, Koolhaas JM, Langhans W, Schulz PE, Siegel J, Tobeña A (1998) Genetic selection and differential stress responses: the Roman lines/strains of rats. Ann N Y Acad Sci 851:501–510. doi: 10.1111/j.1749-6632.1998.tb09029.x CrossRefPubMedGoogle Scholar
  19. Driscoll P, Fernández-Teruel A, Corda MG, Giorgi O, Steimer T (2009) Some guidelines for defining personality differences in rats. In: Kim Y-K (ed) Handbook of behavior genetics. Springer, New York, pp 281–300, ISBN: 978-0-387-76726-0CrossRefGoogle Scholar
  20. Dulawa SC, Holick KA, Gundersen B, Hen R (2004) Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 29:1321–1330. doi: 10.1038/sj.npp.1300433 CrossRefPubMedGoogle Scholar
  21. El Yacoubi M, Bouali S, Popa D, Naudon L, Leroux-Nicollet I, Hamon M, Costentin J, Adrien J, Vaugeois JM (2003) Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression. Proc Natl Acad Sci USA 100:6227–6232. doi: 10.1073/pnas.1034823100 CrossRefPubMedGoogle Scholar
  22. Escorihuela RM, Tobeña A, Driscoll P, Fernández-Teruel A (1995a) Effects of training, early handling, and perinatal flumazenil on shuttle box acquisition in Roman low-avoidance rats: toward overcoming a genetic deficit. Neurosci Biobehav Rev 19:353–367. doi: 10.1016/0149-7634(94)00051-2 CrossRefPubMedGoogle Scholar
  23. Escorihuela RM, Tobeña A, Fernández-Teruel A (1995b) Environmental enrichment and postnatal handling prevent spatial learning deficits in aged hypoemotional (Roman high-avoidance) and hyperemotional (Roman low-avoidance) rats. Learn Memory 2:40–48. doi: 10.1101/lm.2.1.40 CrossRefGoogle Scholar
  24. 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 shuttlebox behaviors. Physiol Behav 67:19–26. doi: 10.1016/S0031-9384(99)00064-5 CrossRefPubMedGoogle Scholar
  25. Fattore L, Piras G, Corda MG, 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. doi: 10.1038/npp.2008.43 CrossRefPubMedGoogle Scholar
  26. Fernández-Teruel A, Driscoll P, Gil L, Aguilar R, Tobeña A, Escorihuela RM (2002a) Enduring effects of environmental enrichment on novelty seeking, saccharin and ethanol intake in two rat lines (RHA/Verh and RLA/Verh) differing in incentive-seeking behavior. Pharmacol Biochem Behav 73:225–231. doi: 10.1016/S0091-3057(02)00784-0 CrossRefPubMedGoogle Scholar
  27. Fernández-Teruel A, Escorihuela RM, Gray JA, Aguilar R, Gil L, Gimenez-Llort L, Tobeña A, Bhomra A, Nicod A, Mott R, Driscoll P, Dawson GR, Flint J (2002b) A quantitative trait locus influencing anxiety in the laboratory rat. Genome Res 12:618–626. doi: 10.1101/gr.203402 PubMedGoogle Scholar
  28. Ferré P, Fernández-Teruel A, Escorihuela RM, Driscoll P, Corda MG, Giorgi O, Tobeña A (1995) Behavior of the Roman/Verh high- and low-avoidance rat lines in anxiety tests: relationship with defecation and self-grooming. Physiol Behav 58:1209–1213. doi: 10.1016/0031-9384(95)02068-3 CrossRefPubMedGoogle Scholar
  29. Fleischmann A, Prolov K, Abarbanel J, Belmaker RH (1995) The effect of transcranial magnetic stimulation of rat brain on behavioral models of depression. Brain Res 699:130–132. doi: 10.1016/0006-8993(95)01018-Q CrossRefPubMedGoogle Scholar
  30. García-Marquez C, Giralt M, Armario A (1987) Long-lasting effects of chronic chlorimipramine treatment of rats on exploratory activity on a hole-board, and on immobility in the forced swimming test. Eur J Pharmacol 142:385–389, PubMed PMID: 3428352CrossRefPubMedGoogle Scholar
  31. Gelfin Y, Gorfine M, Lerer B (1998) Effect of clinical doses of fluoxetine on psychological variables in healthy volunteers. Am J Psychiatry 155:290–292, http://ajp.psychiatryonline.org/cgi/content/full/155/2/290 PubMedGoogle Scholar
  32. Gentsch C, Lichtsteiner M, Driscoll P, Feer H (1982) Differential hormonal and physiological responses to stress in Roman high- and low-avoidance rats. Physiol Behav 28:259–263. doi: 10.1016/0031-9384(82)90072-5 CrossRefPubMedGoogle Scholar
  33. Giorgi O, Valentini V, Piras G, Di Chiara G, Corda MG (1999) Palatable food differentially activates dopaminergic function in the CNS of Roman/Verh lines and strains of rats. Soc Neurosci Meeting Abs Book 25:2152Google Scholar
  34. Giorgi O, Lecca D, Piras G, Driscoll P, Corda MG (2003a) Dissociation between mesocortical dopamine release and fear-related behaviors in two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions. Eur J Neurosci 17:2716–2726. doi: 10.1046/j.1460-9568.2003.02689.x CrossRefPubMedGoogle Scholar
  35. 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 86:422–431. doi: 10.1046/j.1471-4159.2003.01845.x CrossRefPubMedGoogle Scholar
  36. Giorgi O, Piras G, Lecca D, Corda MG (2005) Differential activation of dopamine release in the nucleus accumbens core and shell after acute or repeated amphetamine injections: a comparative study in the Roman high- and low-avoidance rat lines. Neuroscience 135:987–998. doi: 10.1016/j.neuroscience.2005.06.075 CrossRefPubMedGoogle Scholar
  37. 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. Neurosc Biobehav Rev 31:148–163CrossRefGoogle Scholar
  38. Holsboer F (2001) Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy. J Affect Disord 62:77–91. doi: 10.1016/S0165-0327(00)00352-9 CrossRefPubMedGoogle Scholar
  39. Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156:837–841, http://ajp.psychiatryonline.org/cgi/content/full/156/6/837 PubMedGoogle Scholar
  40. Kessler RC (1997) The effects of stressful life events on depression. Annu Rev Psychol 48:191–214. doi: 10.1146/annurev.psych.48.1.191 CrossRefPubMedGoogle Scholar
  41. Krahl SE, Senanayake SS, Pekary AE, Sattin A (2004) Vagus nerve stimulation (VNS) is effective in a rat model of antidepressant action. J Psychiatry Res 38:237–240. doi: 10.1016/j.jpsychires.2003.11.005 CrossRefGoogle Scholar
  42. López-Aumatell R, Vicens-Costa E, Guitart-Masip M, Martínez-Membrives E, Valdar W, Johannesson M, Cañete T, Blázquez G, Driscoll P, Flint J, Tobeña A, Fernández-Teruel A (2009) Unlearned anxiety predicts learned fear: a comparison among heterogeneous rats and the Roman rat strains. Behav Brain Res 202:92–101. doi: 10.1016/j.bbr.2009.03.024 CrossRefPubMedGoogle Scholar
  43. López-Rubalcava C, Lucki I (2000) Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test. Neuropsychopharmacology 22:191–199. doi: 10.1038/sj.npp.1395424 CrossRefPubMedGoogle Scholar
  44. Lucki I (1997) The forced swimming test as a model for core and component behavioural effects of antidepressant drugs. Behav Pharmacol 8:523–532, http://journals.lww.com/behaviouralpharm/Abstract/1997/11000 CrossRefPubMedGoogle Scholar
  45. Moreno M, Cardona D, Gómez MJ, Sánchez-Santed F, Tobeña A, Fernández-Teruel A, Campa L, Suñol C, Escarabajal MD, Torres C, Flores P (2010) Impulsivity characterization in the roman high- and low-avoidance rat strains: behavioral and neurochemical differences. Neuropsychopharmacology 35:1198–1208. doi: 10.1038/npp.2009.224 CrossRefPubMedGoogle Scholar
  46. Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59:1151–1159. doi: 10.1016/j.biopsych.2005.09.018 CrossRefPubMedGoogle Scholar
  47. Nil R, Bättig K (1981) Spontaneous maze ambulation and Hebb-Williams learning in Roman high-avoidance and Roman low-avoidance rats. Behav Neural Biol 33:465–475, PMID: 7332509CrossRefPubMedGoogle Scholar
  48. Overstreet DH (1993) The Flinders sensitive line rats: a genetic animal model of depression. Neurosci Biobehav Rev 17:51–68. doi: 10.1016/S0149-7634(05)80230-1 CrossRefPubMedGoogle Scholar
  49. Paré WP (1989) “Behavioral despair” test predicts stress ulcer in WKY rats. Physiol Behav 46:483–487. doi: 10.1016/0031-9384(89)90025-5 CrossRefPubMedGoogle Scholar
  50. Piras G, Lecca D, Corda MG, Giorgi O (2003) Repeated morphine injections induce behavioural sensitization in Roman high- but not in Roman low-avoidance rats. Neuroreport 14:2433–2438, http://journals.lww.com/neuroreport/pages/articleviewer.aspx?year=2003&issue=12190&article=00029&type=abstract CrossRefPubMedGoogle Scholar
  51. Poldinger W (1963) Comparison between imipramine and desipramine in normal subjects and their action in depressive patients. Psychopharmacologia 4:302–307. doi: 10.1007/BF00408186 CrossRefGoogle Scholar
  52. Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732. doi: 10.1038/266730a0 CrossRefPubMedGoogle Scholar
  53. Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391, PMID: 204499CrossRefPubMedGoogle Scholar
  54. Pucilowski O, Overstreet DH (1993) Effect of chronic antidepressant treatment on responses to apomorphine in selectively bred rat strains. Brain Res Bull 32:471–475. doi: 10.1016/0361-9230(93)90293-K CrossRefPubMedGoogle Scholar
  55. Siegel J (1997) Augmenting and reducing of visual evoked potentials in high- and low-sensation seeking humans, cats, and rats. Behav Genet 27:557–563. doi: 10.1023/A:1021409132320 CrossRefPubMedGoogle Scholar
  56. 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 6:87–100. doi: 10.1080/1025389031000111320 CrossRefPubMedGoogle Scholar
  57. Steimer T, Python A, Schulz PE, Aubry JM (2007) Plasma corticosterone, dexamethasone (DEX) suppression and DEX/CRH tests in a rat model of genetic vulnerability to depression. Psychoneuroendocrinology 32:575–579. doi: 10.1016/j.psyneuen.2007.03.012 CrossRefPubMedGoogle Scholar
  58. Tizabi Y, Copeland RL Jr, Brus R, Kostrzewa RM (1999) Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142:193–1939CrossRefPubMedGoogle Scholar
  59. Vieira C, De Lima TC, Carobrez Ade P, Lino-de-Oliveira C (2008) Frequency of climbing behavior as a predictor of altered motor activity in rat forced swimming test. Neurosci Lett 445:170–173. doi: 10.1016/j.psyneuen.2007.03.012 CrossRefPubMedGoogle Scholar
  60. Walker CD, Rivest RW, Meaney MJ, Aubert ML (1989) Differential activation of the pituitary-adrenocortical axis after stress in the rat: use of two genetically selected lines (Roman low- and high-avoidance rats) as a model. J Endocrinol 123:477–485. doi: 10.1677/joe.0.1230477 CrossRefPubMedGoogle Scholar
  61. Weiss JM, Cierpial MA, West CH (1998) Selective breeding of rats for high and low motor activity in a swim test: toward a new animal model of depression. Pharmacol Biochem Behav 61:49–66. doi: 10.1016/S0091-3057(98)00075-6 CrossRefPubMedGoogle Scholar
  62. Willner P (2005) Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 52:90–110. doi: 10.1159/000087097 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Giovanna Piras
    • 1
  • Osvaldo Giorgi
    • 1
  • Maria G. Corda
    • 1
  1. 1.Department of ToxicologyUniversity of CagliariCagliariItaly

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