The question may be raised as to whether or not the selection for acute withdrawal was for a fundamentally different phenotype than the STSB selection reported by Metten et al. (1998b). This selection has been described in some detail. The lines were found to also differ in withdrawal convulsions after the administration of diazepam, nitrous oxide, zolpidem, and pentobarbital; the lines did not differ in threshold convulsant sensitivity to pentylenetetrazol, N-methyl-d-aspartate, or kainic acid (Metten et al. 1998b). These data were taken to indicate that the selection was not simply for a general difference in CNS activation but rather for some features associated with the mechanisms of action of the depressant drugs. Given the mechanisms of action of these drugs, a GABAergic mechanism is strongly implicated (see, e.g., Mihic et al. 1997; Buck and Finn 2001). In the current study, the High and Low acute withdrawal lines were also found to differ (and in the appropriate direction) for withdrawal after acute pentobarbital administration (Fig. 3).
