Thiamine and benfotiamine counteract ultrasound-induced aggression, normalize AMPA receptor expression and plasticity markers, and reduce oxidative stress in mice

Neuropharmacology. 2019 Sep 15:156:107543. doi: 10.1016/j.neuropharm.2019.02.025. Epub 2019 Feb 25.


The negative societal impacts associated with the increasing prevalence of violence and aggression is increasing, and, with this rise, is the need to understand the molecular and cellular changes that underpin ultrasound-induced aggressive behavior. In mice, stress-induced aggression is known to alter AMPA receptor subunit expression, plasticity markers, and oxidative stress within the brain. Here, we induced aggression in BALB/c mice using chronic ultrasound exposure and examined the impact of the psychoactive anti-oxidant compounds thiamine (vitamin B1), and its derivative benfotiamine, on AMPA receptor subunit expression, established plasticity markers, and oxidative stress. The administration of thiamine or benfotiamine (200 mg/kg/day) in drinking water decreased aggressive behavior following 3-weeks of ultrasound exposure and benfotiamine, reduced floating behavior in the swim test. The vehicle-treated ultrasound-exposed mice exhibited increases in protein carbonyl and total glutathione, altered AMPA receptor subunits expression, and decreased expression of plasticity markers. These ultrasound-induced effects were ameliorated by thiamine and benfotiamine treatment; in particular both antioxidants were able to reverse ultrasound-induced changes in GluA1 and GluA2 subunit expression, and, within the prefrontal cortex, significantly reversed the changes in protein carbonyl and polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression levels. Benfotiamine was usually more efficacious than thiamine. Thus, the thiamine compounds were able to counteract ultrasound-induced aggression, which was accompanied by the normalization of markers that have been showed to be associated with ultrasound-induced aggression. These commonly used, orally-active compounds may have considerable potential for use in the control of aggression within the community. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

Keywords: Aggression; Brain oxidative stress; Emotional stress; Mice; Plasticity; Thiamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / drug effects*
  • Aggression / physiology*
  • Aggression / radiation effects
  • Animals
  • Antioxidants / administration & dosage*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / radiation effects
  • Depression / physiopathology
  • Male
  • Mice, Inbred BALB C
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / radiation effects
  • Oxidative Stress / drug effects*
  • Oxidative Stress / radiation effects
  • Receptors, AMPA / metabolism*
  • Receptors, AMPA / radiation effects
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin / radiation effects
  • Thiamine / administration & dosage*
  • Thiamine / analogs & derivatives*
  • Ultrasonic Waves


  • Antioxidants
  • Receptors, AMPA
  • Receptors, Serotonin
  • serotonin 6 receptor
  • Thiamine
  • benphothiamine