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Abstract
Most mice ethanol sensitization studies focused on neurobiology at the expense of its behavioral characterization. Furthermore, relatively short ethanol exposures (10 to 20 injections) were used in these studies. The first aim of the present study is to better characterize the development and expression of ethanol sensitization after an extended exposure of 45 daily injections. In some previous studies, mice were classified as “respondent” and “resistant” to ethanol sensitization. The second aim of the present study is to test the long-term reliability of such categorizations and the consequences of their use on the interpretation of the ethanol sensitization results. Swiss and DBA/2J female mice received 45 consecutive daily ethanol administrations (respectively 2.5 and 2.0 g/kg) and their locomotor activity was daily recorded to test the development of ethanol sensitization. At the end of the procedure, a challenge test assessed the inter-group ethanol sensitization.The results of the present study show that ethanol sensitization continues to develop beyond 20 days to reach maximal levels after about 25 injections in DBA/2J mice and 40 injections in Swiss mice, although the core phase of the development of ethanol sensitization occurred in both strains during the first 20 days. Remarkably, ethanol sensitization after such a long daily ethanol treatment resulted in both an upward shift of the magnitude of ethanol stimulant effects and a prolongation of these effects in time (up to 30 minutes). Mice classified as “resistant to ethanol sensitization” according to previous studies developed very significant levels of ethanol sensitization when tested after 45 ethanol injections and are best described as showing a delayed development of ethanol sensitization. Furthermore, mice classified as respondent or resistant to ethanol sensitization also differ in their acute response to ethanol, such that it is difficult to ascertain whether these classifications are specifically related to the sensitization process.
Highlights
Repeated administrations of addictive drugs induce gradual changes in some of their behavioral effects
Data are expressed as mean ± SEM. (A) shows the acquisition of behavioral sensitization in mice daily injected with ethanol or saline. p
The stimulant effects of ethanol continued to sensitize when the number of ethanol injections exceeded what was usually administered in previously published studies
Summary
Repeated administrations of addictive drugs induce gradual changes in some of their behavioral effects. The gradual and long lasting behavioral increase is termed “behavioral sensitization”. Drug-induced behavioral sensitization is generally modeled as a progressive increase in the locomotor stimulant effects over repeated administrations of the same drug dose [1,2]. Chronic exposure to ethanol has been shown to induce a strong and robust sensitization in mice [3,4] and mice are the most widely used animal model to study ethanol sensitization. Despite some promising results [7,8], such a role of ethanol sensitization clearly needs further confirmations from human studies. Behavioral sensitization is a good experimental tool to explore the neuronal plasticity induced by chronic ethanol exposure
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