Skip to main content
SpringerLink
Log in

Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

A battery of tests designed to elicit reactions to a variety of non-painful threat stimuli was used to study the effects of chlordiazepoxide (5–20 mg/kg), diazepam (1–5 mg/kg) and midazolam (1–10 mg/kg) on the defensive repertoire of wild Rattus rattus. The most consistent effect of benzodiazepine treatment, across compounds and tests, was a marked reduction in defensive threat and attack behaviors, with midazolam effective over a wider range of situations. In contrast, effects on freezing and flight reactions were more variable, differing substantially as a function of stimulus context. The general profile of observed changes in defense cannot be explained in terms of either non-specific behavioral suppression or a global reduction in defensiveness. Rather, our findings suggest that benzodiazepines may primarily induce a shift within the defense repertoire.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Avis HH (1974) The neuropharmacology of aggression: a critical review. Psychol Bull 81:47–63.

    Google Scholar 

  • Baxter BL (1964) The effect of chlordiazepoxide on the hissing response elicited via hypothalamic stimulation. Life Sci 3:531–537.

    Google Scholar 

  • Beattie CW, Chernov HI, Bernard PS, Glenny FH (1969) Pharmacological alteration of hyperreactivity in rats with septal and hypothalamic lesions. Int J Neuropharmacol 8:365–371.

    Google Scholar 

  • Beattie IA, Berry PA, Lister RE (1970) Methods for detecting anti-anxiety drugs using baboons (Papio cynocephalus). Br J Pharmacol 38:460P

    Google Scholar 

  • Blanchard RJ, Blanchard DC (1977) Aggressive behavior in the rat. Behav Biol 21:197–224.

    Google Scholar 

  • Blanchard DC, Blanchard RJ (1984) Affect and aggression: an animal model applied to human behavior. In: Blanchard RJ, Blanchard DC (eds) Advances in the study of aggression, vol I. Academic Press, New York

    Google Scholar 

  • Blanchard RJ, Blanchard DC (1987) An ethoexperimental approach to the study of fear. Psychol Rec 37:305–316.

    Google Scholar 

  • Blanchard DC, Blanchard RJ (1988) Ethoexperimental approaches to the biology of emotion. Annual Rev Psychol: 39. Annual Reviews, Palo Alto, USA

    Google Scholar 

  • Blanchard RJ, Blanchard DC, Takahashi T, Kelley M (1977) Attack and defensive behaviour in the albino rat. Anim Behav 25:622–634.

    Google Scholar 

  • Blanchard DC, Blanchard RJ, Lee EMC, Williams G (1981a) Taming of the wild Norway rat following lesions in the basal ganglia. Physiol Behav 27:995–1000.

    Google Scholar 

  • Blanchard DC, Williams G, Lee EMC, Blanchard RJ (1981b) Taming of wild Rattus norvegicus by lesions of the mesencephalic gray. Physiol Psychol 9:157–163.

    Google Scholar 

  • Blanchard RJ, Kleinschmidt CK, Flannelly KJ, Blanchard DC (1984) Fear and aggression in the rat. Aggress Behav 10:309–315.

    Google Scholar 

  • Blanchard RJ, Flannelly KJ, Blanchard DC (1986a) Defensive behaviors of laboratory and wild Rattus norvegicus. J Comp Psychol 100:101–107.

    Google Scholar 

  • Blanchard RJ, Blanchard DC, Flannelly KJ, Hori K (1986b) Ethanol changes patterns of defensive behavior in wild rats. Physiol Behav 38:645–650.

    Google Scholar 

  • Blanchard DC, Hori K, Rodgers RJ, Hendrie CA, Blanchard RJ (1988) Differential effects of 5HT1a agonists and benzodiazepines on defensive patterns in wild Rattus rattus. In: Bevan P, Olivier B, Archer T (eds) Behavioral Pharmacology of 5-HT. (in press)

  • Blyther S, Marriott AS (1969) The effects of drugs on the hyperreactivity or rats with bilateral anterior hypothalamic lesions. Br J Pharmacol 37:507P-508P

    Google Scholar 

  • Cameron DB, Blampied NM (1980) Rat's reactions to a predator: modification by chlordiazepoxide. NZ Psychol 9:9–13.

    Google Scholar 

  • Chance MRA, Silverman AP (1964) The structure of social behaviour and drug action. In: Steinberg H, de Reuck AVS (eds) Animal behaviour and drug action. Churchill Livingstone. London, pp 65–79.

    Google Scholar 

  • Christmas AJ, Maxwell DR (1970) A comparison of the effects of some benzodiazepines and other drugs on aggressive and exploratory behaviour in mice and rats. Neuropharmacology 9:17–29.

    Google Scholar 

  • Coutinho CB, King M, Carbone JJ, Manning JE, Boff E, Crews T (1971) Chlordiazepoxide metabolism as related to the reduction in aggressive behaviour of cynomolgus primates. Xenobiotica 1:287–301.

    Google Scholar 

  • Dantzer R (1977) Behavioural effects of benzodiazepines: a review. Biobehav Revs 1:71–86.

    Google Scholar 

  • File SE (1987) The search for novel anxiolytics. TINS 10:461–463.

    Google Scholar 

  • Goldberg ME (1970) Pharmacologic activity of a new class of agents which selectively inhibit aggressive behaviour in rats. Arch Int Pharmacodyn Ther 186:287–297.

    Google Scholar 

  • Graeff FG, Brandao ML, Audi EA, Schultz MTB (1986) Modulation of the brain aversive system by GABAergic and serotonergic mechanisms. Behav Brain Res 21:65–72.

    Google Scholar 

  • Heise GA, Boff E (1961) Taming action of chlordiazepoxide. Fed Proc 20:393.

    Google Scholar 

  • Heuschele WP (1961) Chlordiazepoxide for calming zoo animals. J Am Vet Med Assoc 139:996.

    Google Scholar 

  • Hoffmeister F, Wuttke W (1969) On the actions of psychotropic drugs on attack- and aggressive-defensive behaviour of mice and cats. In: Carattini S, Sigg EB (eds) Aggressive behaviour. Excerpta Medica, Amsterdam, pp 273–280.

    Google Scholar 

  • Horovitz ZP, Furgiuele AR, Brannick LJ, Burke JC, Craver BN (1963) A new chemical structure with specific depressant effects on the amygdala and on the hyper-irritability of the “septal rat”. Nature 200:369–370.

    Google Scholar 

  • Irwin W, Kinohi R, Van Sloten M, Workman MP (1971) Drug effects on distress-evoked behaviour in mice: methodological and drug class comparisons. Psychopharmacologia 20:172–185.

    Google Scholar 

  • Kemble ED, Blanchard DC, Blanchard RJ, Takushi R (1984) Taming in wild rats following medial amygdaloid lesions. Physiol Behav 32:131–134.

    Google Scholar 

  • Krsiak M (1975) Timid singly-housed mice: their value in prediction of psychotropic activity of drugs. Br J Pharmacol 55:141–150.

    Google Scholar 

  • Krsiak M (1979) Effects of drugs on behaviour of aggressive mice. Br J Pharmacol 65:525–533.

    Google Scholar 

  • Krsiak M, Sulcova A, Tomasikova Z, Dlohozkova N, Kosar E, Masek K (1981) Drug effects of attack, defense and escape in mice. Pharmacol Biochem Behav [Suppl 1] 14:47–52.

    Google Scholar 

  • Krsiak M, Sulcova A, Donat P, Tomasikova Z, Dlohozkova N, Kosar E, Masek K (1984) Can social and agonistic interactions be used to detect anxiolytic activity of drugs. In: Miczek KA, Kruk MR, Olivier B (eds) Ethopharmacological aggression research. Liss, New York, pp 93–114.

    Google Scholar 

  • Langfeldt T, Ursin H (1971) Differential action of diazepam on flight and defense behaviour in the cat. Psychopharmacologia 19:61–66.

    Google Scholar 

  • Lister RE, Beattie IA, Berry PA (1971) Effects of drugs on social behaviour of baboons. In: Vinar O, Votava Z, Bradley PB (eds) Advances in neuropsychopharmacology. North-Holland, London, pp 299–303.

    Google Scholar 

  • Malick JB (1970) Effects of selected drugs on stimulus-bound emotional behaviour elicited by hypothalamic stimulation in the cat. Arch Int Pharmacodyn Ther 186:137–141.

    Google Scholar 

  • Manning FJ, Elsmore TF (1972) Shock-elicited fighting and delta 9-tetrahydrocannabinol. Psychopharmacologia 25:218–228.

    Google Scholar 

  • Miczek KA (1974) Intraspecies aggression in rats: effects of d-amphetamine and chlordiazepoxide. Psychopharmacologia 39:275–301.

    Google Scholar 

  • Miczek KA (1987) The psychopharmacology of aggression. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 19. Plenum Press, New York, pp 183–328.

    Google Scholar 

  • Miczek KA, Barry H (1976) Pharmacology of sex and aggression. In: Glick SD, Goldfarb J (eds) Behavioral pharmacology. Mosby, St. Louis, pp 176–257.

    Google Scholar 

  • Miczek KA, Krsiak M (1979) Drug effects on agonistic behaviour. Adv Behav Pharmacol 2:87–162.

    Google Scholar 

  • Mos J, Olivier B (1987) Pro-aggressive actions of benzodiazepines. In: Olivier B, Mos J, Brain PF (eds) Ethopharmacology of agonistic behavior in animals and humans. Nijhoff, Dordrecht, pp 187–206.

    Google Scholar 

  • Mos J, Olivier B, van der Poel AM (1987) Modulatory actions of benzediazepine receptor ligands on agonistic behavior. Physiol Behav 41:265–278.

    Google Scholar 

  • Murasaki M, Hora T, Oguchi T, Inami A, Ikeda Y (1976) Action of enpiprazole on emotional behaviour induced by hypothalamic stimulation in rats and cats. Psychopharmacologia 49:271–274.

    Google Scholar 

  • Panksepp J (1971) Drugs and stimulus-bound attack. Physiol Behav 6:317–320.

    Google Scholar 

  • Pieri L (1983) Preclinical pharmacology of midazolam. Br J Clin Pharmacol 16:17S-27S

    Google Scholar 

  • Poole TB (1973) Some studies on the influence of chlordiazepoxide on the social interaction of golden hamsters (Mesocritcetus auratus). Br J Pharmacol 48:538–545.

    Google Scholar 

  • Quenzer LF, Feldman RS, Moore JW (1974) Toward the mechanism of the antiaggression effects of chlordiazepoxide in rats. Psychopharmacologia 34:81–94.

    Google Scholar 

  • Randall LO (1960) Pharmacology of methaminodiazepoxide. Dis Nerv Syst 21:7–10.

    Google Scholar 

  • Randall LO, Schallek W (1967) Pharmacological activity of certain benzodiazepines. In: Efron DH (ed) Psychopharmacology: a review of progress 1957–1967. United States Public Health Service Pub. No. 1836, pp 153–171

  • Randall LO, Schallek W, Heise GA, Keith EF, Bagdon RE (1959) The psychosedative properties of methaminodiazepoxide. J Pharmacol Exp Ther 129:163–171.

    Google Scholar 

  • Robichaud RC, Goldberg ME (1974) Pharmacological properties of two chlordiazepoxide metabolites following microsomal enzyme inhibition. Arch Int Pharmacodyn Ther 211:165–173.

    Google Scholar 

  • Rodgers RJ (1981) Drugs, aggression and behavioral methods. In: Brain PF, Benton D (eds) Multidisciplinary approaches to aggression research. Elsevier/North-Holland, Amsterdam, pp 325–340.

    Google Scholar 

  • Rodgers RJ, Waters AJ (1985) Benzodiazepines and their antagonists: a pharmacoethological analysis with particular reference to effects on “aggression”. Neurosci Biobehav Rev 9:21–35.

    Google Scholar 

  • Schallek W, Kuehn A, Jew N (1962) Effects of chlordiazepoxide (Librium) and other psychotropic agents on the limbic system of the brain. Ann NY Acad Sci 96:303–314.

    Google Scholar 

  • Scheckel CL, Boff E (1967) Effects of drugs on aggressive behaviour in monkeys. In: Brill H, Cole JO, Deniker P, Hippius H, Bradley PB (eds) Neuropsychopharmacology. Excepta Medica, Amsterdam, pp 789–795.

    Google Scholar 

  • Senault B (1970) Comportement d'agressivite intraspecifique induit par l'apomorphine chez le rat. Psychopharmacologia 18:271–287.

    Google Scholar 

  • Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw Hill, New York

    Google Scholar 

  • Sofia RD (1969) Effects of centrally-active drugs on four models of experimentally-induced aggression in rodents. Life Sci 8:705–716.

    Google Scholar 

  • Stark P, Henderson JK (1966) Differentiation of classes of neurosedatives using rats with septal lesions. Int J Neuropharmacol 5:385–389.

    Google Scholar 

  • Takahashi L, Blanchard RJ (1982) Attack and defense in laboratory and wild Norway and black rats. Behav Proc 7:49–62.

    Google Scholar 

  • Tedeschi DH, Fowler PJ, Miller RB, Macko E (1969) Pharmacological analysis of footshock-induced fighting behaviour. In: Garattini S, Sigg EB (eds) Aggressive behaviour. Excerpta Medica, Amsterdam, pp 245–252.

    Google Scholar 

  • Treit D (1985) Animal models for the study of anti-anxiety agents: a review. Neurosci Biobehav Rev 9:203–222.

    Google Scholar 

  • Treit D, Lolordo VM, Armstrong DE (1986) The effects of diazepam on “fear” reactions in rats are modulated by environmental constraints on the rat's defensive repertoire. Pharmacol Biochem Behav 25:561–565.

    Google Scholar 

  • Yoshimura H, Ogawa N (1984) Pharmaco-ethological analysis of agonistic behaviour between resident and intruder mice: effects of psychotropic drugs. Folia Pharm Japonica 84:221–228.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bekesy Laboratory of Neurobiology, University of Hawaii, 96822, Honolulu, Hawaii

    D. Caroline Blanchard & Robert J. Blanchard

  2. Department of Psychology, University of Hawaii, 96822, Honolulu, Hawaii

    Kevin Hori & Robert J. Blanchard

  3. Department of Psychology, University of Bradford, BD7 1DP, Bradford

    R. John Rodgers & Colin A. Hendrie

Authors
  1. D. Caroline Blanchard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. John Rodgers
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Colin A. Hendrie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert J. Blanchard
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Blanchard, D.C., Hori, K., Rodgers, R.J. et al. Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines. Psychopharmacology 97, 392–401 (1989). https://doi.org/10.1007/BF00439457

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00439457

Key words

Search

Navigation