Trait anxiety and ethanol: Anxiolysis in high-anxiety mice and no relation to intake behavior in an addiction model

Abstract

Anxiety has been proposed to play a role in the development of alcohol addiction, but the exact mechanisms by which this occurs remain unclear. The present study aimed to verify the relationship between basal anxiety levels, the anxiolytic-like effect of ethanol, and ethanol intake in mice exposed to an addiction model. In one experiment Swiss mice were characterized as high-anxiety (HA), medium-anxiety (MA), or non-anxiety (NA) in the elevated plus maze and then received saline or ethanol 2 g/kg acutely and chronically and were again exposed to the same test. NA mice decreased while MA mice maintained anxiety indices over the test days, regardless of treatment. HA ethanol-treated mice showed an anxiolytic-like effect, both acutely and chronically, while the saline-treated ones maintained their basal anxiety levels. In another experiment HA and MA mice were exposed to an addiction model based on a 3-bottle free-choice paradigm (ethanol 5% and 10%, and water) consisting of four phases: acquisition (10 weeks), withdrawal (W, 2 weeks), reexposure (2 weeks), and quinine-adulteration (2 weeks). HA and MA control mice had access only to water. Mice were characterized as addicted, heavy-drinker and light-drinker [Fachin-Scheit DJ, Ribeiro AF, Pigatto G, Goeldner FO, Boerngen-Lacerda R. Development of a mouse model of ethanol addiction: naltrexone efficacy in reducing consumption but not craving. J Neural Transm 2006;113:1305-21.]. No difference was observed between HA and MA mice in their preference for and intake of ethanol. No correlation was observed between ethanol intake, during any phase, and anxiety indices measured in the basal tests and during the W phase. The differences in anxiety indices between HA and MA groups persisted in the test performed during ethanol withdrawal, suggesting a "trait" anxiety profile. The data suggest that despite the fact that high anxiety trait levels are important for the anxiolytic-like effects of ethanol, they are not a determining factor for high ethanol intake, at least not under these experimental conditions.

Categories of Wistar Rats Based on Anxiety Traits: A Study Using Factor and Cluster Method

“…A medium level of anxiety, normally observed in rodents, based on the free-exploratory paradigm [23] and EPM test [24], is consistent with the finding of the present study. In the present study, rats displaying medium level of anxiety spent 10-50% of the test time in the open arm of EPM which may be considered as normal anxiety trait in rats according to previous report [20].…”

Predictors of ethanol consumption in adult Sprague–Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake

“…Selectively bred rats that show high anxiety in an open field are found to consume more ethanol at concentrations of 6% or 10% (Izidio and Ramos, 2007), but not at 2% or 4% (Da Silva et al, 2004). Further, studies in outbred rodents using an elevated plus maze have also demonstrated a positive relationship (Spanagel et al, 1995), although this was not confirmed in a recent study in Swiss mice (Correia et al, 2009). …”

High-Anxious Individuals Show Increased Chronic Stress Burden, Decreased Protective Immunity, and Increased Cancer Progression in a Mouse Model of Squamous Cell Carcinoma

“…Anxiety Classification: The EPM and LDA tests quantify anxiety-related behaviors by creating conditions that tap into the intrinsic conflicts arising from the innate tendency of mice to explore (in order to increase the probability of finding food, water, and sex) and the innate fear/anxiety generated during exploration of well-lit, exposed, or elevated areas, which increases the probability of being attacked or killed by a predator or conspecific aggressor. These arenas have been used to measure trait anxiety in mice [114]–[116]. We used data from two ethological tests (EPM and LDA) because each test is thought to measure a different dimension of anxiety [92].…”