Time-dependent quantifiable withdrawal from ethanol in the rat: effect of method of dependence induction.

The importance of temporal factors on the presence and severity of ethanol withdrawal signs in the rat was quantified using rating scale, tremor, and acoustic startle paradigms. Ethanol dependence was induced in naive male Wistar rats by liquid diet administration (n = 21) or vapor inhalation (n = 13). Subjects were analyzed for intensity and duration of physiological ethanol dependence in repeated-measures trials conducted over 72 h post-ethanol withdrawal. Indices of dependence included CNS hyperexcitability manifested as observable withdrawal signs increased acoustic startle reactivity, and tremor activity. Data analysis revealed that withdrawal signs, observed and elicited, generally reached peak intensities between 12 and 24 h postwithdrawal and were more readily observed following vapor inhalation than liquid diet administration, probably because of the higher BALs attained with the inhalation procedure. Results suggest a difference in time course observed with the different behavioral paradigms. In particular, a possible sensitization to startle stimuli was exhibited independent of both startle intensity and dependence induction method. The neural substrates governing these behavioral time course differences remain to be determined.