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The guinea pig forced swim test as a new behavioral despair model to characterize potential antidepressants

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Abstract

Rationale

Behavioral despair is a model of high predictivity for antidepressant activity in murids. For some drug targets, guinea pigs exhibit a higher homology to their human counterparts compared to murids.

Objectives

In this paper, we established a model of behavioral despair namely, the forced swim test (FST) in guinea pigs.

Materials and methods

Male guinea pigs underwent the FST similar to rats. Animals received intraperitoneal injections of either vehicle or drugs 24, 4, and 0.5 h before testing. We tested the tricyclic antidepressants desipramine and amitriptyline, the monoamine oxidase inhibitor tranylcypromine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, and the neurokinin 1 (NK1) receptor antagonist, L-733,060, and for comparison the antipsychotic clozapine and the stimulant methamphetamine.

Results

Desipramine (≥3 mg/kg) and amitriptyline (>10 mg/kg) increased the latency to immobility (LTI) to greater than 230 s, and tranylcypromine (10 mg/kg) it to greater than 190 s. Paroxetine (>0.3 mg/kg) and fluoxetine (>10 mg/kg) also increased LTI significantly but only to greater than 120 s. Methamphetamine (3 mg/kg) completely eliminated immobility, whereas clozapine (5–20 mg/kg) had no effect. L-733,060 (10 mg/kg) increased LTI to 270 s. Doses producing significant effects in FST were investigated in the open field. Antidepressants did not affect locomotion, whereas methamphetamine induced hyperlocomotion.

Conclusions

We demonstrate the suitability of a modified procedure of the FST for a nonmurid species: the guinea pig. Known antidepressants showed similar effects as in rats and mice. It is interesting to note that the NK1 antagonist L-733,060 increased forced swimming, suggesting its antidepressant potential. Thus, the guinea pig FST allows the study of antidepressant activity also in NK1 antagonists that cannot be studied appropriately in murids.

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References

  • Becker LA, Hennessy MB (1993) Further characterization of the behavioral effects of peripherally administered corticotropin-releasing factor in guinea pigs. Pharmacol Biochem Behav 44:925–930

    Article  PubMed  CAS  Google Scholar 

  • Beresford IJ, Birch PJ, Hagan RM, Ireland SJ (1991) Investigation into species variants in tachykinin NK1 receptors by use of the non-peptide antagonist, CP-96,345. Br J Pharmacol 104:292–293

    PubMed  CAS  Google Scholar 

  • Capelozzi MA, Leick-Maldonado EA, Parra ER, Martins MA, Tiberion IF, Capelozzi VL (2007) Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model. Respir Physiol Neurobiol 156:171–178

    Article  PubMed  CAS  Google Scholar 

  • Carlezon WA, Pliakasa AM, Parowa AM, Detkea MJ, Cohena BM, Renshawa PF (2002) Antidepressant-like effects of cytidine in the forced swim test in rats. Biol Psychiatr 51:882–889

    Article  CAS  Google Scholar 

  • Chaki S, Nakazato A, Kennis L, Nakamura M, Mackie C, Sugiura M, Vinken P, Ashton D, Langlois X, Steckler T (2004) Anxiolytic- and antidepressant-like profile of a new CRF1 receptor antagonist, R278995/CRA0450. Eur J Pharmacol 485:145–158

    Article  PubMed  CAS  Google Scholar 

  • Cryan JF, Markou A, Lucki I (2002) Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 23:238–245

    Article  PubMed  CAS  Google Scholar 

  • Detke MJ, Lucki I (1996) Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: the effects of water depth. Behav Brain Res 73:43–46

    Article  PubMed  CAS  Google Scholar 

  • Dymond KE, Fewell JE (1999) Gender influences the core temperature response to a simulated open field in adult guinea pigs. Physiol Behav 65:889–892

    Article  PubMed  CAS  Google Scholar 

  • Einat H, Kronfeld-Schor N, Eilam D (2006) Sand rats see the light: short photoperiod induces a depression-like response in a diurnal rodent. Behav Brain Res 173:153–157

    Article  PubMed  Google Scholar 

  • Gordon MN, Muller CD, Sherman KA, Morgan DG, Azzaro AJ, Wecker L (1999) Oral versus transdermal selegiline: antidepressant-like activity in rats. Pharmacol Biochem Behav 63:501–506

    Article  PubMed  CAS  Google Scholar 

  • Haemisch A (1990) Coping with social conflict, and short-term changes of plasma cortisol titers in familiar and unfamiliar environments. Physiol Behav 47:1265–1270

    Article  PubMed  CAS  Google Scholar 

  • Hudzik TJ, Yanek M, Porrey T, Evenden J, Paronis C, Mastrangelo M, Ryan C, Ross S, Stenfors C (2003) Behavioral pharmacology of AR-A000002, a novel, selective 5-hydroxytryptamine1B antagonist. J Pharmacol Exp Ther 304:1072–1084

    Article  PubMed  CAS  Google Scholar 

  • Keller M, Montgommery S, Ball W, Morrison M, Snavely D, Liu G, Hargreaves R, Hietala J, Lines C, Beebe K, Reines S (2006) Lack of efficacy of the substance P (Neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry 59:216–223

    Article  PubMed  CAS  Google Scholar 

  • Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E, Hale JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Carlson EJ, Hargreaves RJ, Rupniak NM (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281:1640–1645

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Lucki I (1997) The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol 8:523–532

    Article  PubMed  CAS  Google Scholar 

  • Lucki I, Dalvi A, Mayorga AJ (2001) Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology 155:315–322

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ, Newman-Tancredi A, Rivet JM, Brocco M, Lacroix P, Audinot V, Cistarelli L, Gobert A (1997) S-15535, a novel benzodioxopiperazine ligand of serotonin (5-HT)1A receptors: I. Interaction with cloned human (h)5-HT1A, dopamine hD2/hD3 and halpha2A-adrenergic receptors in relation to modulation of cortical monoamine release and activity in models of potential antidepressant activity. J Pharmacol Exp Ther 282:132–147

    PubMed  CAS  Google Scholar 

  • Oksenberg D, Marsters SA, Odowd BF, Jin H, Havlik S, Peroutka SJ, Ashkenazi A (1992) A single amino acid difference confers major pharmacological variation between human and rodent 5-HT1B receptors. Nature 360:161–163

    Article  PubMed  CAS  Google Scholar 

  • Pliakas AM, Carlson RR, Neve RL, Konradi C, Nestler EJ, Carlezon WA Jr (2001) Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens. J Neurosci 21:7397–7403

    PubMed  CAS  Google Scholar 

  • Porsolt RD (2000) Animal models of depression: utility for transgenic research. Rev Neurosci 11:53–58

    PubMed  CAS  Google Scholar 

  • Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732

    Article  PubMed  CAS  Google Scholar 

  • Porsolt RD, Anton G, Blavet N, Jalfre M (1978a) Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391

    Article  CAS  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1978b) “Behavioural despair” in rats and mice: strain differences and the effects of imipramine. Eur J Pharmacol 51:291–294

    Article  CAS  Google Scholar 

  • Pradier L, Habert-Ortoli E, Emile L, Le Guern J, Loquet I, Bock MD, Clot J, Mercken L, Fardin V, Garret C (1995) Molecular determinants of the species selectivity of neurokinin type 1 receptor antagonists. Mol Pharmacol 47:314–321

    PubMed  CAS  Google Scholar 

  • Rex A, Marsden CA, Fink H (1993) Effect of diazepam on cortical 5-HT release and behaviour in the guinea-pig on exposure to the elevated plus maze. Psychopharmacology 110:490–496

    Article  PubMed  CAS  Google Scholar 

  • Sanchez C, Meier E (1997) Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike. Psychopharmacology 129:197–205

    Article  PubMed  CAS  Google Scholar 

  • Shimazoe T, Shibatat S, Ueki S (1987) A new forced swimming test for the evaluation of antidepressants in rats by recording vibration of a water tank. J Pharmacobiodyn 10:639–643

    PubMed  CAS  Google Scholar 

  • Shimazu S, Minami A, Kusumoto H, Yoneda F (2005) Antidepressant-like effects of selegiline in the forced swim test. Eur Neuropsychopharmacol 15:563–571

    Article  PubMed  CAS  Google Scholar 

  • Stenfors C, Hallerbäck T, Larsson L-G, Wallsten C, Ross SB (2004) Pharmacology of a novel selective 5-hydroxytryptamine1B receptor antagonist, AR-A000002. Naunyn Schmiedebergs Arch Pharmacol 369:330–337

    Article  PubMed  CAS  Google Scholar 

  • Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370

    Article  PubMed  CAS  Google Scholar 

  • Varty GB, Cohen-Williams ME, Hunter JC (2002a) The antidepressant-like effects of neurokinin NK1 receptor antagonists in a gerbil tail suspension test. Behav Pharmacol 14:87–95

    Google Scholar 

  • Varty GB, Cohen-Williams ME, Morgan CA, Pylak U, Duffy RA, Lachowicz JE, Carey GJ, Coffin VL (2002b) The Gerbil elevated plus-maze II: anxiolytic-like effects of selective neurokinin NK1 receptor antagonists. Neuropsychopharmacology 27:371–379

    Article  CAS  Google Scholar 

  • Wilber CG (1957) Influence on temperature on performance in guinea pigs. Am J Physiol 190:457–458

    PubMed  CAS  Google Scholar 

  • Wilber CG (1959) Some factors which are correlated with swimming capacity in guinea pigs. J Appl Physiol 14:199–203

    PubMed  CAS  Google Scholar 

  • Wong M-L, Licinio J (2001) Research and treatment approaches to depression. Nat Rev Neurosci 2:343–351

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Neuroscience Discovery Research, Abbott, 67008, Ludwigshafen, Germany

    Karsten M. Wicke, Ana Jongen-Relo, Ilona Groth & Gerhard Gross

  2. Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, 14195, Berlin, Germany

    Andre Rex

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  1. Karsten M. Wicke
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  2. Andre Rex
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  3. Ana Jongen-Relo
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  4. Ilona Groth
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  5. Gerhard Gross
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Correspondence to Karsten M. Wicke.

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Wicke, K.M., Rex, A., Jongen-Relo, A. et al. The guinea pig forced swim test as a new behavioral despair model to characterize potential antidepressants. Psychopharmacology 195, 95–102 (2007). https://doi.org/10.1007/s00213-007-0874-0

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  • DOI: https://doi.org/10.1007/s00213-007-0874-0

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