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 chro nic ethanol withdrawal severity and acoustic startle response (ASR) in repl icated 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 differen ces 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 c hambers and exposed to a series of white noise stimuli of different intensi ties. Tn Experiment 1, two parameters [the maximal acoustic startle respons e (R-max), and the sound intensity necessary to produce 50% of the maximal startle response (dB(50))] were obtained from a least-squares nonlinear reg ression by fitting data for each subject to a sigmoidal function that best described the relationship between sound intensity and mean ASR. Response h abituation of WSP and WSR mice to a repeated acoustic stimulus of high inte nsity was examined in Experiment 2. Results: When ASR amplitude was plotted versus sound intensity, the sigmoid intensify-response curves of both WSP replicates were shifted to the right relative to the responses of WSR mice, which suggested decreased startle s ensitivity in the WSP animals. Statistical analysis showed that naive WSP m ice were less sensitive (higher dB(50)) to acoustic stimulation than Seizur e-Resistant animals whereas R-max was similar for both lines. The selected lines also differed in their responses to repeated acoustic stimulation, wi th WSP mice demonstrating greater habituation. Conclusion: Results of the present study suggest some common genetic mechan isms underlying behavioral responsiveness to acoustic stimulation and sever ity of ethanol withdrawal.