Skip to main content
SpringerLink
Log in

The effect of α2 adrenoceptor blockers on aggressive behavior in mice: implications for the actions of adrenoceptor agents

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

Abstract

The effects of three α2 adrenoceptor blockers (idazoxan, yohimbine and CH-38083) on isolation-induced aggressive behavior was studied in male mice. The three drugs produced different behavioral profiles. Idazoxan reduced aggressiveness dose-dependently by decreasing the duration of offensive/aggressive interactions and increasing the duration of defensive behaviors. The other two drugs produced only parts of the dual action of idazoxan: yohimbine affected mainly defensive behaviors, while CH-38083 affected only the time spent with fighting. Saline injections per se also influenced behavior and, in contrast to α2 adrenoceptor blockers, induced an increase in aggressiveness. These results are different from those previously obtained in rats, which show bell-shaped dose-response curves in response to α2 adrenoceptor blockers (small doses increased, while large doses decreased aggression). It is postulated that the strong behavioral reaction of mice to the injection per se may mask the aggression-heightening effects of small doses of α2 adrenoceptor blockers in this species. A theory is also presented regarding the complexity of adrenoceptor interactions when both pre-, and postsynaptic α2 adrenoceptors are blocked.

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

  • Barrett JA, Shaikh MB, Edinger H, Siegel A (1987) The effects of intrahypothalamic injections of norepinephrine upon affective defense behavior in the cat. Brain Res 426:381–384

    Article  PubMed  Google Scholar 

  • Barrett JA, Edinger H, Siegel A (1990) Intrahypothalamic injections of norepinephrine facilitate feline affective aggression via alpha 2-adrenoceptors. Brain Res 525:285–293

    Article  PubMed  Google Scholar 

  • Bell R, Hepper PG (1987) Catecholamines and aggression in animals. Behav Brain Res 23:1–21

    Article  PubMed  Google Scholar 

  • Berlan M, Montrasuc J-L, Lafontan M (1992) Pharmacological prospects for α2-adrenoceptor antagonist therapy. Trends Pharmacol Sci Rev 13:277–282

    Article  Google Scholar 

  • Berridge CW, Dunn AJ (1989) Restraint-stress-induced changes in exploratory behavior appear to be mediated by norepinephrine-stimulated release of CRF. J Neurosci 9:3513–3521

    PubMed  Google Scholar 

  • Blanchard RJ, Taukulis HK, Rodgers RJ, Magee LK, Blanchard DC (1993) Yohimbine potentiates active defensive responses to threatening stimuli in Swiss-Webster mice. Pharmacol Biochem Behav 44:673–681

    Article  PubMed  Google Scholar 

  • Cai B, Matsumoto K, Ohta H, Watanabe H (1993) Biphasic effects of typical antidepressants and mianserin, an atypical antidepressant, on aggressive behavior in socially isolated mice. Pharmacol Biochem Behav 44:519–525

    Article  PubMed  Google Scholar 

  • Cole JC, Burroughs GJ, Laverty CR, Sheriff NC, Sparham EA, Rodgers RJ (1995) Anxiolytic-like effects of yohimbine in the murine plus-maze: strain independence and evidence against alpha 2-adrenoceptor mediation. Psychopharmacology 118:425–436

    Article  PubMed  Google Scholar 

  • Cutler MG (1993) Comparison of the effects of yohimbine and clonidine on the behaviour of female mice during social encounters in an “approach-avoidance” situation. Neuropharmacology 32:411–417

    Article  PubMed  Google Scholar 

  • Edens FW (1987) Agonistic behavior and neurochemistry in grouped Japanese quail. Comp Biochem Physiol A 86:473–479

    Article  PubMed  Google Scholar 

  • Erdbrugger W, Raulf M, Otto T, Michel MC (1995) Does [3H]2-methoxy-idazoxan (RX 821002) detect more alpha-2-adrenoceptor agonist high-affinity sites than [3H]rauwolscine? A comparison of nine tissues and cell lines. J Pharmacol Exp Ther 273:1287–1294

    PubMed  Google Scholar 

  • Ferrari F, Giuliani D (1993) Influence of idazoxan on the dopamine D2 receptor agonist-induced behavioural effects in rats. Eur J Pharmacol 250:51–57

    Article  PubMed  Google Scholar 

  • Ferrari F, Cassinadri M, Tartoni PL, Tampieri A (1991) Effects of B-HT 920 in the tail-suspension test. Pharmacol Res 24:75–81

    Article  PubMed  Google Scholar 

  • Garcia-Sevilla JA, Sastre M, Escriba PV (1995) Age-dependent increases of immunoreactive imidazoline receptors in the human brain: possible association of a 29/30 kDa protein with the I2-imidazoline receptor identified by [3H]idazoxan. Neurosci Lett 184:133–136

    Article  PubMed  Google Scholar 

  • Gentsch C, Lichteiner M, Feer H (1989) Behavioral effects of yohimbine and chlordiazepoxide: dependence on the rat's previous familiarization with the test conditions. Neuropsychobiology 22:101–107

    PubMed  Google Scholar 

  • Gorman AL, Dunn AJ (1993) Beta-adrenergic receptors are involved in stress-related behavioral changes. Pharmacol Biochem Behav 45:1–7

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Hadfield MG, Milio C (1988) Isolation-induced fighting in mice and related regional brain monoamine utilization. Behav Brain Res 31:93–96

    Article  PubMed  Google Scholar 

  • Haller J (1993) Adrenomedullar catecholamine liberation and carbohydrate metabolism during the first 30 minutes of an aggressive encounter in rats. Physiol Behav 54:195–197

    Article  PubMed  Google Scholar 

  • Haller J (1995a) Alpha-2 adrenoceptor blockade and the response to intruder aggression in Long-Evans rats. Physiol Behav 58:101–106

    Article  PubMed  Google Scholar 

  • Haller J (1995b) Catecholamine stimulation and the response to behavioral challenge in Wistar rats. Pharmacol Biochem Behav 51:789–794

    Article  PubMed  Google Scholar 

  • Haller J, Makara GB (1996) The preparation for, and the control of aggression by catecholamines. The hormones and the neurotransmitter. Neurosci Biobehav Rev (submitted)

  • Haller J, Barna I, Kovács JL (1994) Alpha-2 adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats. Psychopharmacology 115:478–484

    PubMed  Google Scholar 

  • Haller J, Barna I, Baranyi M (1995a) Hormonal and metabolic responses during psychosocial stimulation in aggressive and nonaggressive rats. Psychoneuroendocrinology 20:65–74

    Article  PubMed  Google Scholar 

  • Haller J, Kiem DT, Makara GB (1995b) Do alpha-2 adrenoceptors modify coping strategies in rats? Psychopharmacology 122:379–385

    Article  PubMed  Google Scholar 

  • Harsing LG Jr, Vizi ES (1991) Evidence that two stereochemically different alpha-2 adrenoceptors modulate norepinephrine release in rat cerebral cortex. J Pharmacol Exp Ther 256:44–49

    PubMed  Google Scholar 

  • Hieble JP, Ruffolo RR Jr (1995) Possible structural and functional relationships between imidazoline receptors and alpha 2-adrenoceptors. Ann NY Acad Sci 763:8–21

    PubMed  Google Scholar 

  • Kacsoh B, Opp JS, Crowley WR, Grosvenor CE (1993) Interaction between the alpha 2-adrenergic system and nursing in the regulation of growth hormone secretion in the neonatal rat. Acta Endocrinol 128:184–191

    PubMed  Google Scholar 

  • Kemble ED, Behrens M, Rawleigh JM, Gibson BM (1991) Effects of yohimbine on isolation-induced aggression, social attraction, and conspecific odor preference in mice. Pharmacol Biochem Behav 40:781–785

    Article  PubMed  Google Scholar 

  • King PR, Gundlach AL, Louis WJ (1995) Quantitative autoradiographic localization in rat brain of alpha 2-adrenergic and non-adrenergic I-receptor binding sites labelled by [3H]rilmenidine. Brain Res 675:264–278

    Article  PubMed  Google Scholar 

  • Levine ES, Litto WJ, Jacobs BL (1990) Activity of cat locus coeruleus noradrenergic neurons during the defense reaction. Brain Res 531:189–195

    Article  PubMed  Google Scholar 

  • Lorton D, Davis JN (1987) The distribution of beta-1- and beta-2-adrenergic receptors of normal and reeler mouse brain: an in vitro autoradiographic study. Neuroscience 23:199–210

    Article  PubMed  Google Scholar 

  • Martti L, Attila J, Etemadzadeh E, Ahtee L (1987) Differences in the effects of morphine on the alpha-methyl-p-tyrosine-induced depletion of dopamine and noradrenaline in various areas of the mouse brain. Pharmacol Toxicol 61:26–32

    PubMed  Google Scholar 

  • Matsumoto K, Cai B, Satoh T, Ohta H, Watanabe H (1991) Desipramine enhances isolation-induced aggressive behavior in mice. Pharmacol Biochem Behav 39:167–170

    Article  PubMed  Google Scholar 

  • Matsumoto K, Ojima K, Ohta H, Watanabe H (1994) Beta 2- but not beta 1-adrenoceptors are involved in desipramine enhancement of aggressive behavior in long-term isolated mice. Pharmacol Biochem Behav 49:13–18

    Article  PubMed  Google Scholar 

  • Mogilnicka E, Zazula M (1986) Interaction between beta-adrenoceptor agonists and alpha 1-adrenergic system. A behavioral study with the clonidine-induced aggression test. Pol J Pharmacol Pharm 38:529–534

    PubMed  Google Scholar 

  • Neylon CB, Summers RJ (1985) [3H]-rauwolscine binding to alpha 2-adrenoceptors in the mammalian kidney: apparent receptor heterogeneity between species. Br J Pharmacol 85:349–359

    PubMed  Google Scholar 

  • Peterson JT, Pohorecky LA, Hamm MW (1989) Neuroendocrine and beta-adrenoceptor response to chronic ethanol and aggression in rats. Pharmacol Biochem Behav 34:247–253

    Article  PubMed  Google Scholar 

  • Poncet MF, Damase-Michel C, Tavernier G, Tran MA, Berlan M, Montastruc JL, Montastruc P (1992) Changes in plasma catecholamine and neuropeptide Y levels after sympathetic activation in dogs. Br J Pharmacol 105:181–183

    PubMed  Google Scholar 

  • Portillo M, Reverte M, Langin D, Senard JM, Tran MA, Berlan M, Montastruc JL (1991) Effect of a 7-day treatment with idazoxan and its 2-methoxy derivative RX 821002 on alpha 2-adrenoceptors and non-adrenoceptor idazoxan binding sites in rabbits. Br J Pharmacol 104:190–194

    PubMed  Google Scholar 

  • Rawleigh JM, Kemble ED (1992) Test-specific effects of FG-7142 on isolation-induced aggression in mice. Pharmacol Biochem Behav 42:317–321

    Article  PubMed  Google Scholar 

  • Shishkina GT, Borodin PM, Naumenko EB (1990) The noradrenaline content and the alpha 2-adrenoreceptor count in the brain of brown rats selected for the absence of aggressive behavior in relation to man. Zh Vyssh Nerv Deiat Im I P Pavlova 40:326–330

    PubMed  Google Scholar 

  • Soderpalm B, Engel JA (1990) Alpha 1- and beta-adrenoceptor stimulation potentiate the anticonflict effect of a benzodiazepine. J Neural Transm [Gen Sect] 79:155–167

    Article  Google Scholar 

  • Vizi ES, Harsing LG Jr, Gaal J, Kapocsi J, Bernath S, Somogyi GT (1986) CH-38083, a selective, potent antagonist of alpha-2 adrenoceptors. J Pharmacol Exp Ther 238:701–706

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hungarian Academy of Science, Institute of Experimental Medicine, P.O. Box 67, H-1450, Budapest, Hungary

    J. Haller, G. B. Makara & J. L. Kovács

Authors
  1. J. Haller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. B. Makara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. L. Kovács
    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

Haller, J., Makara, G.B. & Kovács, J.L. The effect of α2 adrenoceptor blockers on aggressive behavior in mice: implications for the actions of adrenoceptor agents. Psychopharmacology 126, 345–350 (1996). https://doi.org/10.1007/BF02247386

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02247386

Key words

Search

Navigation