Effects of training, early handling, and perinatal flumazenil on shuttle box acquisition in Roman low-avoidance rats: toward overcoming a genetic deficit.

The present series of studies investigated the effects of intensive training, postnatal handling-stimulation and/or perinatal flumazenil (Ro 15-1788, benzodiazepine receptor antagonist) on the acquisition of two-way active avoidance by Roman low-avoidance (RLA/Verh) rats. This rat line has been selectively bred for poor avoidance in the shuttle box, while their Roman high-avoidance counterparts (RHA/Verh) have been selectively bred for their extremely good performance in that task. In the first experiment, RLA/Verh rats submitted to a long and intensive training procedure (unlike those submitted to short training) were able to achieve a performance of 56% of avoidances per session. In the second experiment both postnatal handling and perinatal flumazenil treatments increased avoidance responding in another group of RLA/Verh rats tested at the age of 18 months. Finally, in the last experiment, the performance of a third stock of RLA/Verh rats of the same age which had received perinatal flumazenil did not differ, on the later phases of training, from that shown by RHA/Verh animals. The results are discussed in terms of the "warm up" phenomena which seems to be highly involved in the selection of RLA/Verh rats, as well as on the possibility that central benzodiazepine receptors could play a role in the genetic deficit shown by RLA/Verh rats, which apparently confers a greater emotivity.