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Social approach–avoidance behavior of a high-anxiety strain of rats: effects of benzodiazepine receptor ligands

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Abstract

Rationale

To better understand anxiety disorders with social impairments as well as to identify new treatments, it is important to develop preclinical procedures involving social components of anxiety. Recently, a novel procedure was reported: the rat Social Approach–Avoidance (SAA) test. In this test, the time spent by a test rat in a large social compartment containing an unfamiliar stimulus rat reflects the anxiety state of the animal. It was shown that prestressing the test rat increased the avoidance of the social compartment as characterized by an increase in the time spent in the nonsocial compartment.

Objective

(1) To use a high-anxiety strain, F-344 rats, instead of prestressed animals, (2) to automate the test by using video tracking to measure time spent in both compartments and their subdivisions, and (3) to validate this modified test with known benzodiazepine receptor ligands.

Materials and methods

F-344 rats were treated with either chlordiazepoxide or diazepam (benzodiazepine receptor agonists), or RO 19-4603 or FG 7142 (benzodiazepine receptor inverse agonists).

Results

The agonists produced anxiolytic-like effects, whereas the inverse agonists produced anxiogenic-like effects. These effects were most marked in the two extreme zones in terms of distance to the stimulus rat.

Conclusions

F-344 rats display spontaneous avoidance behavior in the modified SAA procedure, and approach–avoidance behavior in these rats is sensitive to benzodiazepine agonists and inverse agonists in a bidirectional manner. The finding that the assessment of time spent into two virtual zones in each of the compartments markedly increased the sensitivity to both anxiolytics and anxiogenics will be discussed using the concept of physical defensive distance.

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References

  • Bandelow B, Zohar J, Hollander E, Kasper S, Moller HJ (2002) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive–compulsive and posttraumatic stress disorders. World J Biol Psychiatry 3:171–199

    Article  PubMed  Google Scholar 

  • Belzung C, Misslin R, Vogel E (1990) Anxiogenic effects of a benzodiazepine receptor partial inverse agonist, RO 19-4603, in a light/dark choice situation. Pharmacol Biochem Behav 36:593–596

    Article  PubMed  CAS  Google Scholar 

  • Bert B, Fink H, Huston JP, Voits M (2002) Fischer 344 and Wistar rats differ in anxiety and habituation but not in water maze performance. Neurobiol Learn Mem 78:11–22

    Article  PubMed  Google Scholar 

  • Berton O, Ramos A, Chaouloff F, Mormde P (1997) Behavioral reactivity to social and nonsocial stimulations: a multivariate analysis of six inbred rat strains. Behav Genet 27:155–166

    Article  PubMed  CAS  Google Scholar 

  • Brodkin ES, Hagemann A, Nemetski SM, Silver LM (2004) Social approach–avoidance behavior of inbred mouse strains towards DBA/2 mice. Brain Res 1002:151–157

    Article  PubMed  CAS  Google Scholar 

  • Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, Wehner JM, Wynshaw-Boris A, Paylor R (1997) Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology (Berl) 132:107–124

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • File SE, Pellow S, Braestrup C (1985) Effects of the beta-carboline, FG 7142, in the social interaction test of anxiety and the holeboard: correlations between behaviour and plasma concentrations. Pharmacol Biochem Behav 22:941–944

    Article  PubMed  CAS  Google Scholar 

  • File SE, Seth P (2003) A review of 25 years of the social interaction test. Eur J Pharmacol 463:35–53

    Article  PubMed  CAS  Google Scholar 

  • Gray JA, McNaughton N (2000) Ethology and anxiety. In: Gray JA, McNaughton N (eds) The Neuropsychology of anxiety, 2nd edn. Oxford Psychology Series, Oxford University Press, Oxford

  • Griebel G, Belzung C, Perrault G, Sanger DJ (2000) Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice. Psychopharmacology (Berl) 148:164–170

    Article  CAS  Google Scholar 

  • Haller J, Bakos N (2002) Stress-induced social avoidance: a new model of stress-induced anxiety? Physiol Behav 77:327–332

    Article  PubMed  CAS  Google Scholar 

  • Haller J, Leveleki C, Baranyi J, Mikics E, Bakos N (2003) Stress, social avoidance and anxiolytics: a potential model of stress-induced anxiety. Behav Pharmacol 14:439–446

    PubMed  CAS  Google Scholar 

  • Herbert JD, Hope DA, Bellack AS (1992) Validity of the distinction between generalized social phobia and avoidant personality disorder. J Abnorm Psychol 101:332–339

    Article  PubMed  CAS  Google Scholar 

  • Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51:8–19

    PubMed  CAS  Google Scholar 

  • Lightowler S, Kennett GA, Williamson IJ, Blackburn TP, Tulloch IF (1994) Anxiolytic-like effect of paroxetine in a rat social interaction test. Pharmacol Biochem Behav 49:281–285

    Article  PubMed  CAS  Google Scholar 

  • Magee WJ, Eaton WW, Wittchen HU, McGonagle KA, Kessler RC (1996) Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry 53:159–168

    PubMed  CAS  Google Scholar 

  • McNaughton N, Corr PJ (2004) A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance. Neurosci Biobehav Rev 28:285–305

    Article  PubMed  Google Scholar 

  • Mormede P, Ramos A (2000) Genetics and emotional behaviors: experimental studies. In: Jones CJ, Mormede P (eds) Neurobehavioral genetics, methods and applications. CRC, Boca Raton, pp 301–315

    Google Scholar 

  • Ramos A, Berton O, Mormede P, Chaouloff F (1997) A multiple-test study of anxiety-related behaviours in six inbred rat strains. Behav Brain Res 85:57–69

    Article  PubMed  CAS  Google Scholar 

  • Ramos A, Mormede P (1998) Stress and emotionality: a multidimensional and genetic approach. Neurosci Biobehav Rev 22:33–57

    Article  PubMed  CAS  Google Scholar 

  • Reich J, Goldenberg I, Vasile R, Goisman R, Keller M (1994) A prospective follow-along study of the course of social phobia. Psychiatry Res 54:249–258

    Article  PubMed  CAS  Google Scholar 

  • Rex A, Voigt JP, Fink H (1999) Behavioral and neurochemical differences between Fischer 344 and Harlan–Wistar rats raised identically. Behav Genet 29:187–192

    Article  PubMed  CAS  Google Scholar 

  • Rex A, Voigt JP, Gustedt C, Beckett S, Fink H (2004) Anxiolytic-like profile in Wistar, but not Sprague–Dawley rats in the social interaction test. Psychopharmacology (Berl) 177:23–34

    Article  CAS  Google Scholar 

  • Sams-Dodd F (1995) Automation of the social interaction test by a video-tracking system: behavioural effects of repeated phencyclidine treatment. J Neurosci Methods 59:157–167

    Article  PubMed  CAS  Google Scholar 

  • Sareen L, Stein M (2000) A review of the epidemiology and approaches to the treatment of social anxiety disorder. Drugs 59:497–509

    Article  PubMed  CAS  Google Scholar 

  • Shulman ID, Cox BJ, Swinson RP, Kuch K, Reichman JT (1994) Precipitating events, locations and reactions associated with initial unexpected panic attacks. Behav Res Ther 32:17–20

    Article  PubMed  CAS  Google Scholar 

  • Toit PL, Stein DJ (2003) Social anxiety disorder. In: Nutt DJ, Ballenger JC (eds) Anxiety disorders. Blackwell, Oxford, pp 95–124

    Google Scholar 

  • Turner SM, Beidel DC, Townsley RM (1992) Social phobia: a comparison of specific and generalized subtypes and avoidant personality disorder. J Abnorm Psychol 101:326–331

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

We thank Françoise Kahn for her excellent technical assistance.

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Correspondence to Eric P. M. Prinssen.

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Nicolas, L.B., Prinssen, E.P.M. Social approach–avoidance behavior of a high-anxiety strain of rats: effects of benzodiazepine receptor ligands. Psychopharmacology 184, 65–74 (2006). https://doi.org/10.1007/s00213-005-0233-y

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  • DOI: https://doi.org/10.1007/s00213-005-0233-y

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