Genetic association between chronic ethanol withdrawal severity and acoustic startle parameters in WSP and WSR mice

Background: The present study examined the genetic association between chronic ethanol withdrawal severity and acoustic startle response (ASR) in replicated lines of mice selected for high (Withdrawal Seizure-Prone; WSP) and low (Withdrawal Seizure-Resistant; WSR) susceptibility to handling- induced convulsions after withdrawal from chronic exposure to ethanol. Any differences on a nonselected (correlated) trait between the opposite-selected lines is strong evidence for pleiotropic effects of the genes fixed by selection. Methods: Naive WSP and WSR mice of both replicates were placed in startle chambers and exposed to a series of white noise stimuli of different intensities. In Experiment 1, two parameters [the maximal acoustic startle response (R(max)), and the sound intensity necessary to produce 50% of the maximal startle response (dB₅₀)] were obtained from a least-squares nonlinear regression by fitting data for each subject to a sigmoidal function that best described the relationship between sound intensity and mean ASR Response habituation of WSP and WSR mice to a repeated acoustic stimulus of high intensity was examined to Experiment 2. Results: When ASR amplitude was plotted versus sound intensity, the sigmoid intensity-response curves of both WSP replicates were shifted to the right relative to the responses of WSR mice, which suggested decreased startle sensitivity in the WSP animals. Statistical analysis showed that naive WSP mice were less sensitive (higher dB₅₀) to acoustic stimulation than Seizure-Resistant animals whereas R(max) was similar for both lines. The selected lines also differed in their responses to repeated acoustic stimulation, with WSP mice demonstrating greater habituation. Conclusion: Results of the present study suggest some common genetic mechanisms underlying behavioral responsiveness to acoustic stimulation and severity of ethanol withdrawal.