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Social instability in female rats: effects on anxiety and buspirone efficacy

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Abstract

Rationale

Buspirone produces inconsistent effects in laboratory rodents. Individual housing increases the efficacy of buspirone in male rats, suggesting that the effects of this (and other) compounds become conspicuous in animals showing anxiety-like states. The effect of individual housing was, however, weak, and evident only when the locomotor suppressive effects of buspirone dissipated (i.e. 4 h after treatment).

Objectives

The effects of social instability, a recently developed model of social stress in female rats, was investigated on both anxiety and the anxiolytic efficacy of buspirone.

Methods

Female rats were exposed to alternate days of isolation and moderate crowding for 2 weeks. Group composition was changed for each crowding phase. Basal anxiety and the anxiolytic efficacy of buspirone were assessed by the social interaction test of anxiety 24 h after the last crowding phase.

Results

Crowding appeared stressful, as it increased plasma glucocorticoid levels in less than 1 h. Anxiety-like behaviours were increased by social instability compared with stable group housing. In group housed controls, buspirone markedly suppressed locomotion, without clear effects on anxiety-related behaviours. Social instability attenuated the locomotor suppressive effects of buspirone, but made the anxiolytic effects of the compound more conspicuous. The effects of individual housing (assessed earlier) and social instability (assessed here) on buspirone efficacy appear qualitatively different.

Conclusions

Buspirone abolishes stress-induced anxiety, but has no anxiolytic effects in controls. This is consistent with clinical findings, as the drug decreases anxiety in anxious patients but not in healthy humans. Laboratory models involving stress-induced anxiety-like states can improve our understanding of drug effects and efficacy.

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References

  • Benton D, Brain PF (1981) Behavioural and adrenocortical reactivity in female mice following individual or group housing. Dev Psychobiol 14:100–107

    Google Scholar 

  • Blanchard DC, Griebel G, Blanchard RJ (1995) Gender bias in the preclinical pharmacology of anxiety. Male models of predominantly female disorders. J Psychopharmacol 9:79–82

    Google Scholar 

  • Bohus B, Koolhaas JM, Korte SM, Bouws GA, Eisenga W, Smit J (1990) Behavioral physiology of serotonergic and steroid-like anxiolytics as antistress drugs. Neurosci Biobehav Rev 14:529–534

    CAS  PubMed  Google Scholar 

  • Bond AJ, Lader MH (1981) Comparative effects of diazepam and buspirone on subjective feelings, psychological tests and the EEG. Int Pharmacopsychiatry 16:212–220

    CAS  PubMed  Google Scholar 

  • Brain PF, Nowell NW (1971) Theeffect of prior housing on adrenal response to isolation/grouping in male albino mice. Psychon Sci 22:183–184

    Google Scholar 

  • Brown KJ, Grunberg NE (1995) Effects of housing on male and female rats: crowding stresses males but calms females. Physiol Behav 58:1085–1089

    Article  CAS  PubMed  Google Scholar 

  • Cheeta S, Irvine E, File SE (2001) Social isolation modifies nicotine’s effects in animal tests of anxiety. Br J Pharmacol 132:1389–1395

    CAS  PubMed  Google Scholar 

  • Collinson N, Dawson GR (1997) On the elevated plus-maze the anxiolytic-like effects of the 5-HT(1A) agonist, 8-OH-DPAT, but not the anxiogenic-like effects of the 5-HT(1A) partial agonist, buspirone, are blocked by the 5-HT1A antagonist WAY 100635. Psychopharmacology 132:35–43

    Google Scholar 

  • Delle Chiaie R, Pancheri P, Casacchia M, Stratta P, Kotzalidis GD, Zibellini M (1995) Assessment of the efficacy of buspirone in patients affected by generalized anxiety disorder, shifting to buspirone from prior treatment with lorazepam: a placebo-controlled, double-blind study. J Clin Psychopharmacol 15:12–19

    Article  PubMed  Google Scholar 

  • Downing RW, Rickels K (1982) The impact of favorable and unfavorable life events on psychotropic drug response. Psychopharmacology 78:97–100

    Google Scholar 

  • File SE, Hyde JRG (1978) Can social interaction be used to measure anxiety? Br J Pharmacol 62:19–24

    Google Scholar 

  • Fluttert M, Dalm S, Oitzl MS (2000) A refined method for sequential blood sampling by tail incision in rats. Lab Anim 34:372–378

    CAS  PubMed  Google Scholar 

  • Gao B, Cutler MG (1993) Buspirone increases social investigation in pair-housed male mice; comparison with the effects of chlordiazepoxide. Neuropharmacology 32:429–437

    Google Scholar 

  • Griebel G, Perrault G, Soubrie P (2001) Effects of SR48968, a selective non-peptide NK2 receptor antagonist on emotional processes in rodents. Psychopharmacology 158:241–251

    Article  CAS  PubMed  Google Scholar 

  • Guy AP, Gardner CR (1985) Pharmacological characterization of a modified social interaction model of anxiety in the rat. Neuropsychobiology 13:194–200

    CAS  PubMed  Google Scholar 

  • Haller J (2001) The link between stress and the efficacy of anxiolytics. A new avenue of research. Physiol Behav 73:337–342

    Article  CAS  PubMed  Google Scholar 

  • Haller J, Fuchs E, Halász J, Makara GB (1999) Defeat is a major stressor in males while social instability is stressful mainly in females: towards the development of a social stress model in female rats. Brain Res Bull 50:33–39

    Article  CAS  PubMed  Google Scholar 

  • Haller J, Halász J, Makara GB (2000) Housing conditions and the anxiolytic efficacy of buspirone: the relationship between main and side effects. Behav Pharmacol 11:403–412

    CAS  PubMed  Google Scholar 

  • Johnston AL, File SE (1986) 5-HT and anxiety: promises and pitfalls. Pharmacol Biochem Behav 24:1467–1470

    CAS  PubMed  Google Scholar 

  • Kofman O, Einat H, Cohen H, Tenne H, Shoshana C (2000) The anxiolytic effect of chronic inositol depends on the baseline level of anxiety. J Neural Transm 107:241–253

    Article  CAS  PubMed  Google Scholar 

  • Koks S, Mannisto PT, Bourin M, Shlik J, Vasar V, Vasar E (2000) Cholecystokinin-induced anxiety in rats: relevance of pre-experimental stress and seasonal variations. J Psychiatr Neurosci 25:33–42

    CAS  Google Scholar 

  • Laaris N, Haj-Dahmane S, Hamon M, Lanfumey L (1995) Glucocorticoid receptor-mediated inhibition by corticosterone of 5-HT1A autoreceptor functioning in the rat dorsal raphe nucleus. Neuropharmacology 34:1201–1210

    CAS  PubMed  Google Scholar 

  • MajercsikE, Haller J, LevelekiC, Baranyi J, Halász J, Rodgers RJ (2004) The effect of social factors on the anxiolytic efficacy of buspirone in male rats, male mice, and men. Prog Neuropsychopharmacol Biol Psychiatry (in press)

  • Man MS, Young AH, McAllister-Williams RH (2002) Corticosterone modulation of somatodendritic 5-HT1A receptor function in mice. J Psychopharmacol 16:245–252

    CAS  PubMed  Google Scholar 

  • Manzaneque JM, Brain PF, Navarro JF (2002) Effect of low doses of clozapine on behaviour of isolated and group-housed male mice in the elevated plus-maze test Prog Neuropsychopharmacol Biol Psychiatry 26:349–355

  • McNaughton N, Panickar KS, Logan B (1996) The pituitary-adrenal axis and the different behavioral effects of buspirone and chlordiazepoxide. Pharmacol Biochem Behav 54:51–56

    CAS  PubMed  Google Scholar 

  • Meijer OC, de Kloet ER (1998) Corticosterone and serotonergic neurotransmission in the hippocampus: functional implications of central corticosteroid receptor diversity. Crit Rev Neurobiol 12:1–20

    CAS  PubMed  Google Scholar 

  • Murasaki M, Miura S, Ishigooka J, Ishii Y, Takahashi A, Fukuyama Y (1989) Phase I study of a new antianxiety drug, buspirone. Prog Neuropsychopharmacol Biol Psychiatry 13:137–144

    Article  CAS  PubMed  Google Scholar 

  • Picinelli M, Simon G (1997) Gender and cross-cultural differences in somatic symptoms associated with emotional distress. An international study in primary care. Psychol Med 27:433–444

    Article  PubMed  Google Scholar 

  • Pokk P, Zharkovsky A (1998) The effects of buspirone on the behavior of control and. stressed mice. J Physiol Pharmacol 49:175–185

    CAS  PubMed  Google Scholar 

  • Rilke O, Freier D, Jahkel M, Oehler J (1998) Dynamic alterations of serotonergic metabolism and receptors during social isolation of low- and high-active mice. Pharmacol Biochem Behav 59:891–896

    Article  CAS  PubMed  Google Scholar 

  • Rodgers RJ (1997) Animal models of “anxiety”: where next? Behav Pharmacol 8:477–496

    CAS  PubMed  Google Scholar 

  • Rush CR, Critchfield TS, Troisi JR, Griffiths RR (1995) Discriminative stimulus effects of diazepam and buspirone in normal volunteers. J Exp Anal Behav 63:277–294

    CAS  PubMed  Google Scholar 

  • Steinberg JR (1994) Anxiety in elderly patients. A comparison of azapirones and benzodiazepines. Drugs Aging 5:335–345

    CAS  PubMed  Google Scholar 

  • Strand M, Hetta J, Rosen A, Sorensen S, Malmstrom R, Fabian C, Marits K, Vetterskog K, Liljestrand AG, Hegen C (1990) A double-blind, controlled trial in primary care patients with generalized anxiety: a comparison between buspirone and oxazepam. J Clin Psychiatry 51:40–45

    Google Scholar 

  • Szadoczky E, Rihmer Z, Papp Z, Furedi J (1997) The prevalence of affective and anxiety disorders in primary care practice in Hungary. J Affect Disord 43:239–244

    Article  CAS  PubMed  Google Scholar 

  • Wurthmann C, Klieser E, Lehmann E, Krauth J (1996) Single-subject experiments to determine individually differential effects of anxiolytics in generalized anxiety disorder. Neuropsychobiology 33:196–201

    CAS  PubMed  Google Scholar 

Download references

Acknowledgement

This work was supported by OTKA grant no. T 032345.

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Authors and Affiliations

  1. Institute of Experimental Medicine, PO Box 67, 1450, Budapest, Hungary

    József Haller, Johanna Baranyi, Nikoletta Bakos & József Halász

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  1. József Haller
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  2. Johanna Baranyi
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  3. Nikoletta Bakos
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  4. József Halász
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Correspondence to József Haller.

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Haller, J., Baranyi, J., Bakos, N. et al. Social instability in female rats: effects on anxiety and buspirone efficacy. Psychopharmacology 174, 197–202 (2004). https://doi.org/10.1007/s00213-003-1746-x

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  • DOI: https://doi.org/10.1007/s00213-003-1746-x

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