Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in Nijmegen Wistar rats.

The aim of the study was to investigate the biphasic locomotor response to ethanol in rats. Based on the recent finding that high responders to novelty (HR) and low responders to novelty (LR), selected from an outbred Nijmegen Wistar rat population, show differences in ethanol intake and preference, it was initially investigated to what extent HR and LR differ in their locomotor response to ethanol. A dose-response curve (0.2-2.0 g/kg, i.p.) was established using standardized activity boxes. HR showed a significant increase at 0.5 g/kg, followed by a significant decrease at doses 1.0-2.0 g/kg; LR showed only a decrease at doses 1.0-2.0 g/kg. Secondly, it was investigated to what extent stress altered the ethanol-induced increase and decrease, respectively. For that purpose, the ethanol-induced locomotor effects (0.5 and 1.0 g/kg) were analyzed in habituated and non-habituated (stressed) HR and LR; habituation consisted of a 15-min adaptation period to the activity cages. Stress significantly enhanced the excitatory effects in HR, but had no effect on the sedative effects in HR and LR. Finally, the locomotor effects of sub-chronic treatment (7 days) with an excitatory (0.5 g/kg) or sedative (1.0 g/kg) dose were analyzed in HR and LR. The excitatory effect of 0.5 g/kg disappeared throughout the treatment in HR, whereas the sedative effects of 1.0 g/kg remained the same in HR and LR. It is concluded that the mechanism underlying the ethanol-induced motor excitation differs completely from that underlying the ethanol-induced sedation. Given the known differences in the make-up of the brain and endocrine system between HR and LR, these animals are suggested to be good models for studying the mechanisms underlying the biphasic locomotor response to ethanol in rats.