July 2006

Document Type


Degree Name



Dept. of Behavioral Neuroscience


Oregon Health & Science University


The effects of multiple ethanol withdrawals on handling-induced convulsions(HICs; HIC singular)and voluntary ethanol ingestion were observed in the Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) Mus musculus selected lines. Vapor inhalation chambers were used to administer single- or multiple-withdrawal treatments (SW or MW, respectively) to WSP and WSR mice, which differed in the number of exposures to 16-h of chronic ethanol vapor inhalation followed by 8-h of air inhalation (SW=one 16-h ethanol vapor treatment per phase, or two treatments total; MW=three 16-h ethanol vapor treatments per phase, or six treatments total). In this design, each single 16-h ethanol:8-h air exposure resulted in a short-term, chronic 16-hintoxication followed by an 8-h withdrawal experience, which resulted in distinct withdrawal histories for each treatment group. Two separate experiments implemented this treatment schedule to explore the effects of a history of numerous alcohol intoxications and withdrawals on two different phenotypes. Experiment 1 examined the possible kindling-like effect of repeated ethanol withdrawals on handling-induced convulsions (HICs) in SW- and MW-treated mice of both WSP and WSR replicates; experiment 2 examined the effect of a withdrawal history on free-choice alcohol drinking in SW- and MW treated mice in replicate 1 of WSP and WSR lines. For both experiments, blood ethanol concentrations were statistically equated prior to analyses. In experiment 1, main effects of treatment supported a kindling-like phenomenon for withdrawal-induced HICs in WSP and WSR lines, where MW groups had significantly greater HICs than SW groups within each line. Cumulative effects of withdrawal were observed in response to repeated treatment administration, though the effect was opposite in WSP and WSR lines: WSP mice showed a kindling-like potentiation of the HIC response during the second phase of the study, where WSR mice had more intense HIC responses during the first phase of experiment 1. Throughout the course of experiment 2, the WSR line voluntarily drank more ethanol than the WSP selected line. Changes in ethanol consumption were observed by line (WSP < WSR) and by treatment (SW >MW); significant within-line treatment effects were observed in the WSR line (SW groups drank more than MW groups), but such effects were absent in the WSP line. Repeated measures analyses gave mixed results, depending on the index used to reference drinking (g/kg/day 10%ethanol consumption or preference ratio). A kindling-like effect was observed for alcohol withdrawal-precipitated HICs, where multiple ethanol withdrawal experiences and repeated administration of treatment phases increased the severity of HICs. An inverse relationship between withdrawal experiences and free-choice alcohol drinking was observed in the WSR selected line, such that animals with multiple withdrawals were found to voluntarily drink less ethanol. These results suggest that the genes influencing HICs in the WSP and WSR selected lines might partially affect alcohol withdrawal induced drinking.




School of Medicine



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