Behavioral Disinhibition and Reduced Anxiety-like Behaviors in Monoamine Oxidase B-Deficient Mice

Abstract

Monoamine oxidase (MAO) B catalyzes the degradation of b-phenylethylamine (PEA), a trace amine neurotransmitter implicated in mood regulation. Although several studies have shown an association between low MAO B activity in platelets and behavioral disinhibition in humans, the nature of this relation remains undefined. To investigate the impact of MAO B deficiency on the emotional responses elicited by environmental cues, we tested MAO B knockout (KO) mice in a set of behavioral assays capturing different aspects of anxiety-related manifestations, such as the elevated plus maze, defensive withdrawal, marble burying, and hole board. Furthermore, MAO B KO mice were evaluated for their exploratory patterns in response to unfamiliar objects and risk-taking behaviors. In comparison with their wild-type (WT) littermates, MAO B KO mice exhibited significantly lower anxiety-like responses and shorter latency to engage in risk-taking behaviors and exploration of unfamiliar objects. To determine the neurobiological bases of the behavioral differences between WT and MAO B KO mice, we measured the brain-regional levels of PEA in both genotypes. Although PEA levels were significantly higher in all brain regions of MAO B KO in comparison with WT mice, the most remarkable increments were observed in the striatum and prefrontal cortex, two key regions for the regulation of behavioral disinhibition. However, no significant differences in transcript levels of PEA's selective receptor, trace amine-associated receptor 1 (TAAR1), were detected in either region. Taken together, these results suggest that MAO B deficiency may lead to behavioral disinhibition and decreased anxiety-like responses partially through regional increases of PEA levels.

Granulocyte-Macrophage Colony-Stimulating Factor Is Neuroprotective in Experimental Traumatic Brain Injury

“…The GM -/-+ LFP mice also displayed abnormal behavior in the elevated-plus maze, spending significantly more time in the open arm compared with the sham-injured groups. The finding of increased time spent on the open arm is consistent with some previous LFP findings, 30 and in the absence of hyperactivity has been interpreted as disinhibitory or impulsive behavior, 30,41 which are symptoms observed in patients post-TBI. 42 Other studies, however, report that rats given a severe LFP injury display a hyperanxious phenotype post-TBI, 33,39 whereas here, the WT + LFP mice did not.…”

Chronic treatment with mood stabilizer lithium inhibits amphetamine-induced risk-taking manic-like behaviors

“…The open field test (OFT), elevated zero maze test or elevated plus maze (EPM) test were previously used to analyze the effect of lithium on risk-taking behaviors in various animal models [10,19,[24][25][26][27]. Wire-beam bridge (WBB) test was used to analyze risk-taking behavior by measuring the tendency of mice to reach for a foodrewarding goal through an unrailed bridge above ground [6]. This behavioral test was not previously used to analyze the effect of lithium on risk-taking behavior.…”

Adrenaline and Noradrenaline: Partners and Actors in the Same Play"

“…The MAO-B knockout mice show behavioural disinhibition and decrease anxiety-like responses partially through a regional increase in -phenylethylamine levels (Bortolato et al, 2009). In contrast to the borderline mental retardation and abnormal behavioural phenotype in subjects with selective MAO-A deficiency and the severe mental retardation in patients with combined MAO-A/MAO-B deficiency and Norrie disease, the MAO-B-deficient human subjects neither exhibited abnormal behaviour nor mental retardation except increased reactivity to stress (Grimsby et al, 1997).…”

“…All regions of the brain of MAO-B-deficient mouse pups showed increased levels ofphenylethylamine (Lenders et al, 1996), especially in striatum and prefrontal cortex (Bortolato et al, 2009). The MAO-B knockout mice show behavioural disinhibition and decrease anxiety-like responses partially through a regional increase in -phenylethylamine levels (Bortolato et al, 2009).…”