Elsevier

Life Sciences

Volume 77, Issue 6, 24 June 2005, Pages 693-706
Life Sciences

Effects of ethanol on locomotor and anxiety-like behaviors and the acquisition of ethanol intake in Lewis and spontaneously hypertensive rats

https://doi.org/10.1016/j.lfs.2005.01.013Get rights and content

Abstract

The purpose of the present study was to investigate whether Lewis (LEW) and spontaneously hypertensive rats (SHR), characterized in numerous behavioral tests as strains with high-anxiety and low-anxiety, respectively, could differ in their sensitivity to the effects of ethanol in the elevated plus maze (EPM) and the open field (OF), two classical models of anxiety/emotionality, as well as in the acquisition of ethanol drinking behavior. It was also of interest to examine the relationship between sweet and bitter fluids preference and ethanol intake. SHR and LEW rats were given saline or ethanol injections (0.6 or 1.2 g/kg, ip.) and tested in the EPM and OF. Subsequently the same animals were given continuous free choice between water and ethanol solution (2–8%). Additional groups of animals were exposed to a free-choice regimen between saccharin (0.002–0.09%) or quinine (0.0001–0.0015%) and water. The low dose of ethanol (0.6 g/kg) induced anxiolytic-like effects and intensive locomotor activation mainly in SHR rats tested in the OF arena. Overall, LEW counterparts were unaffected in OF test. In oral self-administration paradigm, SHR rats consumed significantly more ethanol than LEW rats. Concerning other solutions, SHR rats consumed large amounts of saccharin compared with LEW rats. These data indicate that the SHR preference for ethanol intake may be positively related to their differential sensitivity to the anxiolytic/stimulant effects of ethanol and to the sensitivity of this strain for saccharin reinforcement. In addition, these findings provide evidence that the SHR strain may represent a useful genetic and pharmacological tool to investigate ethanol drinking traits.

Introduction

In recent years there has been growing interest and evidence showing the importance of genetic risk factors in the development of alcoholism (Slutske et al., 2002, Cheng et al., 2004). Special attention is given to possible biologic mediators of genetic influences. Several studies have searched for genetic predictors of a vulnerability toward alcoholism (Reich, 1988, Schuckit, 1986). It has been hypothesized that some alcoholics are predisposed to ethanol drinking behavior because of innate anxiety and clinical and epidemiological studies indicate a strong association between anxiety and ethanol abuse (Regier et al., 1990, Schuckit and Hesselbrock, 1994). A number of possibilities may be advanced to account for this high frequency of co-ocurrence. However, the literature examining the relationship between anxiety and ethanol intake in animal models is highly controversial. For example, there are studies showing that anxiety-related behaviors are positively correlated with ethanol consumption (Stewart et al., 1993, Spanagel et al., 1995, Möller et al., 1997), while other reports did not show this relationship (Viglinskaya et al., 1995, Overstreet et al., 1997, Henniger et al., 2002, Fernández-Teruel et al., 2002). As a result, we recently investigated this matter using Floripa H and L rats, selectively bred for contrasting anxiety responses in the open field test and two inbred strains, Lewis (LEW) and Spontaneously Hypertensive Rats (SHR), which are known to differ significantly from each other when submitted to several behavioral tests of anxiety/emotionality (Da Silva et al., 2004). No relationship between high anxiety and predisposed vulnerability to a higher intake of ethanol was found in these pairs of strains. Indeed, contrary to what was expected, the less anxious SHR rats consumed significantly more ethanol than LEW rats (Da Silva et al., 2004), which are known to be both addiction-prone (Suzuki et al., 1988, Kosten et al., 1994) and highly anxious (Ramos et al., 1997).

Since other measures of behavioral variables reflecting brain function can serve as predictors of vulnerability to the development of drug intake, the present study was undertaken to further examine the influence of the individual differences displayed by SHR and LEW inbred rats in the propensity for ethanol consumption. Thus, the relationship between sensitivity to the effects of ethanol on emotional reactivity assessed in the plus maze and open field tests and the voluntary ethanol drinking in both strains was investigated. It was also of interest to determine whether any predictive relationship existed between sweet and bitter taste preferences and ethanol intake.

Section snippets

Animals

Male LEW and SHR rats weighing approximately 240–300 g (12 weeks old) at the beginning of the experiment, were maintained under controlled temperature (22 ± 1°C), on a light:dark cycle of 12 h with lights on at 07.00 hours and with free access to laboratory food and water. Initially, all rats were group-housed until the completion of the elevated plus-maze and open field tests. When intake of specific solutions was required, rats were housed individually in metal hanging cages. All procedures

Results

Fig. 1 shows the effects of the injection of saline and ethanol (0.6 and 1.2 g/kg) on the behavior of LEW and SHR rats in the elevated plus-maze. The two-way ANOVA for the percentage of time spent on open arms showed a significant main effect of strain (F1,72 = 171.21; P < 0.000001), treatment (F2,72 = 5.15; P < 0.008) and strain/treatment interaction (F2,72 = 2.96; P < 0.05). Confirming previous studies, baselines values displayed by strains for the percentage of time spent in open arms were

Discussion

Comparison of SHR and LEW rats indicated differential sensitivity to ethanol's behavioral effects in two models of emotionality/anxiety. In the EPM, SHR and LEW rats appeared to have similar sensitivities to ethanol's anxiolytic effects as indicated by a selective increase in the time spent in the open arms. However, in the OF test, only SHR significantly increased locomotor activity. Also a gradual increase in voluntary ethanol intake by SHR, a strain known to present least anxiety-related

Acknowledgement

Part of this study was presented at the XXIV CINP Congress, Paris, June 20–24, 2004.

This work was supported by CNPq, CAPES and FUNCITEC-SC, Brazil.

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