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Psychopharmacology

, Volume 139, Issue 1–2, pp 160–168 | Cite as

Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists

  • Klaus A. Miczek
  • Subuhee Hussain
  • Sara Faccidomo
ORIGINAL INVESTIGATION

Abstract

One of the critical mechanisms by which alcohol heightens aggression involves forebrain serotonin (5-HT) systems, possibly via actions on 5-HT1A receptors. The present experiments tested the hypothesis that activating 5-HT1A receptors by selective agonists will block the aggression-heightening effects of ethanol. Initially, the selective antagonist WAY 100635 was used to assess whether or not the changes in aggressive behavior after treatment with 8-OH-DPAT and flesinoxan result from action at the 5-HT1A receptors. Resident male CFW mice engaged in aggressive behavior (i.e. attack bites, sideways threats, tail rattle) during 5-min confrontations with a group-housed intruder male. Quantitative analysis of the behavioral repertoire revealed systematic reductions in all salient elements of aggressive behavior after treatment with 8-OH-DPAT (0.1–0.3 mg/kg, IP) or flesinoxan (0.1–1.0 mg/kg, IP). The 5-HT1A agonists also reduced motor activities such as walking, rearing and grooming, although to a lesser degree. Pretreatment with the antagonist WAY 100635 (0.1 mg/kg, IP) shifted the agonist dose-effect curves for behavioral effects to the right. In a further experiment, oral ethanol (1.0 g/kg, PO) increased the frequency of attacks in excess of 2 SD from their mean vehicle level of attacks in 19 out of 76 resident mice. Low doses of 8-OH-DPAT (0.03–0.3 mg/kg) and flesinoxan (0.1, 0.3, 0.6 mg/kg), given before the ethanol treatment, attenuated the alcohol-heightened aggression in a dose-dependent fashion. By contrast, these low 5-HT1A agonist doses affected motor activity in ethanol-treated resident mice to a lesser degree, suggesting behavioral specificity of these anti-aggressive effects. The current results support the hypothesized significant role of 5-HT1A receptors in the aggression-heightening effects of alcohol. If these effects are in fact due to action at somatodendritic 5-HT1A autoreceptors, then the anti-aggressive effects would be associated with decreased 5-HT neurotransmission.

Key words Agonistic behavior Aggression Alcohol Serotonin 5-HT receptor agonist 5-HT receptor antagonist Motor activity Flesinoxan Anxiolytic Locomotion 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Klaus A. Miczek
    • 1
  • Subuhee Hussain
    • 1
  • Sara Faccidomo
    • 1
  1. 1.Department of Psychology, Tufts University, 490 Boston Avenue, Medford, MA 02155, USAUS

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