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Screening antidepressants in the chick separation-stress paradigm

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Abstract

Rationale

Clinical research has indicated that antidepressants are efficacious in the treatment of anxiety disorders, especially when repeatedly administered. However, few animal models of anxiety are sensitive to antidepressants, a finding that may be due to procedures limited to acute administrations.

Objectives

The purpose of the present research was to further validate the chick separation-stress paradigm as an animal model of anxiety by examining its sensitivity to the monoamine oxidase inhibitor (MAOI) phenelzine (6.25, 12.5, 25.0 mg/kg), the tricyclic antidepressant (TCA) imipramine (5.0, 10.0, 20.0 mg/kg), the selective serotonin reuptake inhibitor (SSRI) citalopram (1.0, 2.5, 5.0 mg/kg), and the norepinephrine reuptake inhibitor (NRI) maprotiline (5.0, 10.0, 20.0 mg/kg) under acute (no pretreatment) or repeated (3 or 6 days pretreatment) administration procedures.

Methods

Following any pretreatment, 8-day-old chicks received their respective vehicle or drug probe injection 15 min before tests in either a “mirror” (low stress) or “no mirror” (high stress) condition for a 180-s isolation period. The dependent measures were distress vocalizations to index separation stress and sleep onset latency to index sedation.

Results

The model was sensitive to acutely administered phenelzine (MAOI), imipramine (TCA), and maprotiline (NRI), but not citalopram (SSRI) and retained its sensitivity to these drug probes across both repeated administration procedures. None of the drug probes possessed any sedative properties.

Conclusions

These results help extend the validity and utility of the chick separation-stress paradigm as an animal model of anxiety by demonstrating its sensitivity to antidepressants under both acute and repeated administration procedures.

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References

  • Baker DG, Diamond BI, Gillette G, Hamner M, Katzelnick D, Keller T, Mellman TA, Pontius E, Rosenthal M, Tucker P et al (1995) A double-blind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder. Psychopharmacology 122:386–389

    Article  PubMed  CAS  Google Scholar 

  • Baldessarini RJ (2001) Drugs and the treatment of psychiatric disorders: depression and anxiety disorders (Chap. 19); drugs and the treatment of psychiatric disorders: psychosis and mania (Chap. 20). In: Hardman JG, Limbird LE, Gilman AG (eds) Goodman and Gilman’s the pharmacological basis of therapeutics. McGraw-Hill, New York, pp 447–520

    Google Scholar 

  • Balestrieri M, Ruggeri M, Bellantuono C (1989) Drug treatment of panic disorder—a critical review of controlled clinical trials. Psychiatr Dev 7:337–350

    PubMed  CAS  Google Scholar 

  • Blake BH (1992) Ultrasonic vocalization and body temperature maintenance in infant voles of three species (Rodentia: Arvicolidae). Dev Psychobiol 25:581–596

    Article  PubMed  CAS  Google Scholar 

  • Blumberg MS, Alberts JR (1990) Ultrasonic vocalizations by rat pups in the cold: an acoustic by-product of laryngeal braking? Behav Neurosci 104:808–817

    Article  PubMed  CAS  Google Scholar 

  • Borsini F, Podhorna J, Marazziti D (2002) Do animal models of anxiety predict anxiolytic-like effects of antidepressants? Psychopharmacology 163:121–141

    Article  PubMed  CAS  Google Scholar 

  • Boyer W (1995) Serotonin uptake inhibitors are superior to imipramine and alprazolam in alleviating panic attacks: a meta-analysis. Int Clin Psychopharmacol 10:45–49

    Article  PubMed  CAS  Google Scholar 

  • Branchi I, Santucci D, Vitale A, Alleva E (1998) Ultrasonic vocalizations by infant laboratory mice: a preliminary spectrographic characterization under different conditions. Dev Psychobiol 33:249–256

    Article  PubMed  CAS  Google Scholar 

  • Brunelli SA, Shair HN, Hofer MA (1994) Hypothermic vocalizations of rat pups (Rattus norvegicus) elicit and direct maternal search behavior. J Comp Psychol 108:298–303

    Article  PubMed  CAS  Google Scholar 

  • Clauer PJ (1998) Brooding of young domestic fowl [Online]. Available at http://www.ext.vt.edu/pubs/poultry/factsheets/5.html

  • Connor KM, Sutherland SM, Tupler LA, Malik ML, Davidson JR (1999) Fluoxetine in post-traumatic stress disorder. Randomised, double-blind study. Br J Psychiatry 175:17–22

    Article  PubMed  CAS  Google Scholar 

  • Dannon PN, Iancu I, Grunhaus L (2002) The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study. Hum Psychopharmacol 17:329–333

    Article  PubMed  CAS  Google Scholar 

  • Davidson J, Kudler H, Smith R, Mahorney SL, Lipper S, Hammett E, Saunders WB, Cavenar JO Jr (1990) Treatment of posttraumatic stress disorder with amitriptyline and placebo. Arch Gen Psychiatry 47:259–266

    PubMed  CAS  Google Scholar 

  • Feltenstein MW, Ford NG, Freeman KB, Sufka KJ (2002) Dissociation of stress behaviors in the chick social-separation-stress procedure. Physiol Behav 75:675–679

    Article  PubMed  CAS  Google Scholar 

  • Feltenstein MW, Lambdin LC, Webb HE, Warnick JE, Khan SI, Khan IA, Acevedo EO, Sufka KJ (2003a) Corticosterone response in the chick separation-stress paradigm. Physiol Behav 78:489–493

    Article  PubMed  CAS  Google Scholar 

  • Feltenstein MW, Lambdin LC, Ganzera M, Dharmaratne HRW, Nanayakkara NPD, Khan IA, Sufka KJ (2003b) Anxiolytic properties of Piper methysticum extract samples and fractions in the chick social-separation-stress procedure. Phytother Res 17:210–216

    Article  PubMed  Google Scholar 

  • Feltenstein MW, Warnick JE, Guth AN, Sufka KJ (2004) The chick separation-stress paradigm: a validation study. Pharmacol Biochem Behav 77:221–226

    Article  PubMed  CAS  Google Scholar 

  • File SE (1987) The contribution of behavioural studies to the neuropharmacology of anxiety. Neuropharmacology 26:877–886

    Article  PubMed  CAS  Google Scholar 

  • Fish EW, Faccidomo S, Gupta S, Miczek KA (2004) Anxiolytic-like effects of escitalopram, citalopram, and R-citalopram in maternally separated mouse pups. Pharmacol Exp Ther 308:474–480

    Article  CAS  Google Scholar 

  • Flecknell P (2002) Replacement, reduction and refinement. ALTEX 19:73–78

    PubMed  Google Scholar 

  • Gluck JP, Bell J (2003) Ethical issues in the use of animals in biomedical and psychopharmocological research. Psychopharmacology 171:6–12

    Article  PubMed  CAS  Google Scholar 

  • Hofer MA, Shair HN (1992) Ultrasonic vocalization by rat pups during recovery from deep hypothermia. Dev Psychobiol 25:511–528

    Article  PubMed  CAS  Google Scholar 

  • Hurst M, Lamb HM (2000) Fluoxetine. A review of its use in anxiety disorders and mixed anxiety and depression. CNS Drugs 14:51–80

    Article  CAS  Google Scholar 

  • Kehne JH, Coverdale S, McCloskey TC, Hoffman DC, Cassella JV (2000) Effects of the CRF(1) receptor antagonist, CP 154,526, in the separation-induced vocalization anxiolytic test in rat pups. Neuropharmacology 39:1357–1367

    Article  PubMed  CAS  Google Scholar 

  • Kent JM, Coplan JD, Gorman JM (1998) Clinical utility of the selective serotonin reuptake inhibitors in the spectrum of anxiety. Biol Psychiatry 44:812–824

    Article  PubMed  CAS  Google Scholar 

  • Kosten TR, Frank JB, Dan E, McDougle CJ, Giller EL Jr (1991) Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine. J Nerv Ment Dis 179:366–370

    Article  PubMed  CAS  Google Scholar 

  • Lambdin LC, Guth AN, Feltenstein MW, Sufka KJ (2002) Validation of the chick social-separation stress procedure as a screen for anxiolytic compounds. Soc Neurosci Abstr 26:571.20

    Google Scholar 

  • Lehr E (1989) Distress call reactivation in isolated chicks: a behavioral indicator with high selectivity for antidepressants. Psychopharmacology 97:145–146

    Article  PubMed  CAS  Google Scholar 

  • Martenyi F, Brown EB, Zhang H, Koke SC, Prakash A (2002) Fluoxetine v. placebo in prevention of relapse in post-traumatic stress disorder. Br J Psychiatry 181:315–320

    Article  PubMed  Google Scholar 

  • McKinney WT (1984) Animal models of depression: an overview. Psychiatr Dev 2:77–96

    PubMed  CAS  Google Scholar 

  • Molewijk HE, Hartog K, van der Poel AM, Mos J, Olivier B (1996) Reduction of guinea pig pup isolation calls by anxiolytic and antidepressant drugs. Psychopharmacology 128:31–38

    Article  PubMed  CAS  Google Scholar 

  • Montgomery SA, Montgomery DB, Fineberg N (1990) Early response with clomipramine in obsessive compulsive disorder—a placebo controlled study. Prog Neuro-Psychopharmacol Biol Psychiatry 14:719–727

    Article  CAS  Google Scholar 

  • Mos J, Olivier B (1989) Ultrasonic vocalizations by rat pups as an animal model for anxiolytic activity: effects of serotonergic drugs. In: Bevan P, Cools AR, Archer T (eds) Behavioural pharmacology of 5-HT. Erlbaum, Hilldale, NJ, pp 361–366

    Google Scholar 

  • NIH (1993) Interagency coordinating committee for the use of animals in research: plan for the use of animals in research. US Government Printing Office, Washington, DC

    Google Scholar 

  • Nutt DJ (1990) The pharmacology of human anxiety. Pharmacol Ther 47:233–266

    Article  PubMed  CAS  Google Scholar 

  • Olivier B, Molewijk HE, van der Heyden JA, van Oorschot R, Ronken E, Mos J, Miczek KA (1998) Ultrasonic vocalizations in rat pups: effects of serotonergic ligands. Neurosci Biobehav Rev 23:215–227

    Article  PubMed  CAS  Google Scholar 

  • Orlans FB (1993) In the name of science: issues in responsible animal research. Oxford University Press, Oxford

    Google Scholar 

  • Panksepp J, Vilberg T, Bean NJ, Coy DH, Kastin AJ (1978) Reduction of distress vocalization in chicks by opiate-like peptides. Brain Res Bull 3:663–667

    Article  PubMed  CAS  Google Scholar 

  • Panksepp J, Bean NJ, Bishop P, Vilberg T, Sahley TL (1980a) Opioid blockade and social comfort in chicks. Pharmacol Biochem Behav 13:673–683

    Article  PubMed  CAS  Google Scholar 

  • Panksepp J, Meeker R, Bean NJ (1980b) The neurochemical control of crying. Pharmacol Biochem Behav 12:437–443

    Article  PubMed  CAS  Google Scholar 

  • Podhorna J, Brown RE (2000) Flibanserin has anxiolytic effects without locomotor side effects in the infant rat ultrasonic vocalization model of anxiety. Br J Pharmacol 130:739–746

    Article  PubMed  CAS  Google Scholar 

  • Pollack MH, Zaninelli R, Goddard A, McCafferty JO, Bellew KM, Burnham DB, Iyengar MK (2001) Paroxetine in the treatment of generalized anxiety disorder: result of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 62:350–357

    Article  PubMed  CAS  Google Scholar 

  • Reist C, Kauffmann CD, Haier RJ, Sangdahl C, DeMet EM, Chicz-DeMet A, Nelson JN (1989) A controlled trial of desipramine in 18 men with posttraumatic stress disorder. Am J Psychiatry 146:513–516

    PubMed  CAS  Google Scholar 

  • Rickels K, Downing R, Schweizer E, Hassman H (1993) Antidepressants for the treatment of generalized anxiety disorder. A placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry 50:884–895

    PubMed  CAS  Google Scholar 

  • Roach JT, Sufka KJ (2003) Characterization of the chick carrageenan response. Brain Res 994:216–225

    Article  PubMed  CAS  Google Scholar 

  • Rodgers RJ, Cao BJ, Dalvi A, Holmes A (1997) Animal models of anxiety: an ethological perspective. Braz J Med Biol Res 30:289–304

    Article  PubMed  CAS  Google Scholar 

  • Rupniak NM, Carlson EC, Harrison T, Oates B, Seward E, Owen S, de Felipe C, Hunt S, Wheeldon A (2000) Pharmacological blockade or genetic deletion of substance P (NK(1)) receptors attenuates neonatal vocalisation in guinea-pigs and mice. Neuropharmacology 39:1413–1421

    Article  PubMed  CAS  Google Scholar 

  • Smith KK, Dharmaratne HRW, Feltenstein MW, Broom SL, Roach JT, Nanayakkara NPD, Khan IA, Sufka KJ (2001) Anxiolytic effects of kava extract and kavalactones in the chick social separation-stress paradigm. Psychopharmacology 155:86–90

    Article  PubMed  CAS  Google Scholar 

  • Stahl SM, Mendels J, Schwartz GE (2002) Effects of reboxetine on anxiety, agitation, and insomnia: results of a pooled evaluation of randomized clinical trials. J Clin Psychopharmacol 22:388–392

    Article  PubMed  CAS  Google Scholar 

  • Stein MB, Fyer AJ, Davidson JR, Pollack MH, Wiita B (1999) Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study. Am J Psychiatry 156:756–760

    PubMed  CAS  Google Scholar 

  • Sufka KJ, Weed NC (1994) Construct validation of behavioral indices of isolation stress and inflammatory nociception in young domestic fowl. Physiol Behav 55:741–746

    Article  PubMed  CAS  Google Scholar 

  • Sufka KJ, Hughes RA, McCormick TM, Borland JL (1994) Opiate effects on isolation stress in domestic fowl. Pharmacol Biochem Behav 49:1011–1015

    Article  PubMed  CAS  Google Scholar 

  • Sufka KJ, Roach JT, Chambliss WJ Jr, Broom SL, Feltenstein MW, Wyandt CM, Zeng L (2001) Anxiolytic properties of botanical extracts in the chick social separation-stress procedure. Psychopharmacology 153:219–224

    Article  PubMed  CAS  Google Scholar 

  • Tyrer P, Seivewright N, Murphy S, Ferguson B, Kingdon D, Barczak P, Brothwell J, Darling C, Gregory S, Johnson AL (1988) The Nottingham study of neurotic disorder: comparison of drug and psychological treatments. Lancet 2:235–240

    Article  PubMed  CAS  Google Scholar 

  • Versiani M, Nardi AE, Mundim FD, Alves AB, Liebowitz MR, Amrein R (1992) Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine. Br J Psychiatry 161:353–360

    Article  PubMed  CAS  Google Scholar 

  • Versiani M, Cassano G, Perugi G, Benedetti A, Mastalli L, Nardi A, Savino M (2002) Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder. J Clin Psychiatry 63:31–37

    PubMed  CAS  Google Scholar 

  • Warnick JE, McCurdy CR, Sufka KJ (in press) Opioid receptor function in social attachment in young domestic fowl. Behav Brain Res

  • Watson GS, Sufka KJ (1996) Chlordiazepoxide reverses social-separation-induced distress vocalizations and analgesia in young domestic fowl. Exp Clin Psychopharmacol 4:347–353

    Article  CAS  Google Scholar 

  • Watson GS, Roach JT, Sufka KJ (1999) Benzodiazepine receptor function in the chick social separation-stress procedure. Exp Clin Psychopharmacol 7:83–89

    Article  PubMed  CAS  Google Scholar 

  • Willner P (1991) Behavioral models in psychopharmacology. In: Willner P (ed) Behavioral models in psychopharmacology: theoretical, industrial, and clinical perspectives. Cambridge University Press, Cambridge, MA, pp 3–18

    Google Scholar 

  • Wingerson D, Nguyen C, Roy-Byrne PP (1992) Clomipramine treatment for generalized anxiety disorder. J Clin Psychopharmacol 12:214–215

    Article  PubMed  CAS  Google Scholar 

  • Winslow JT, Insel TR (1990) Serotonergic and catecholaminergic reuptake inhibitors have opposite effects on the ultrasonic isolation calls of rat pups. Neuropsychopharmacology 3:51–59

    PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Jason Warnick, Courtney Cartwright, Laurel Johnson, Emily Mathis, Rob Robertson, April Stewart, and Robert Wicks for providing expert technical assistance, Drs. Michael Allen, Chris McCurdy, and Karen Sabol for their insightful discussions of this project, and Cal-Maine Foods for their generous donation of research animals. This work was supported by the Psychopharmacology Laboratory and an award to MWF from the Graduate School at the University of Mississippi.

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Correspondence to Matthew W. Feltenstein.

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Feltenstein, M.W., Sufka, K.J. Screening antidepressants in the chick separation-stress paradigm. Psychopharmacology 181, 153–159 (2005). https://doi.org/10.1007/s00213-005-2227-1

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