Exposure to certain acute and chronic stressors results in an immediate behavioral and physiological response to the situation followed by a period of days when cross-sensitization to further novel stressors is observed. Cross-sensitization affects to different behavioral and physiological systems, more particularly to the hypothalamus-pituitary-adrenal (HPA) axis. It appears that the nature of the initial (triggering) stressor plays a major role, HPA cross-sensitization being more widely observed with systemic or high-intensity emotional stressors. Less important appears to be the nature of the novel (challenging) stressor, although HPA cross-sensitization is better observed with short duration (5–15 min) challenging stressors. In some studies with acute immune stressors, HPA sensitization appears to develop over time (incubation), but most results indicate a strong initial sensitization that progressively declines over the days. Sensitization can affect other physiological system (i.e. plasma catecholamines, brain monoamines), but it is not a general phenomenon. When studied concurrently, behavioral sensitization appears to persist longer than that of the HPA axis, a finding of interest regarding long-term consequences of traumatic stress. In many cases, behavioral and physiological consequences of prior stress can only be observed following imposition of a new stressor, suggesting long-term latent effects of the initial exposure.

Although noncompetitive NMDA receptor antagonists have shown an anxiolyticlike profile in several studies, such effects have not been observed consistently. Previous studies with ketamine, a noncompetitive NMDA antagonist, have employed only shock tests of anxiety based on conflict procedures. In the present experiment, the effect of an acute low dose of ketamine (7 mg/kg) was examined in adult male Wistar rats tested in three nonconflict tests: holeboard, social interaction, and elevated plus‐maze paradigms. The results showed that ketamine decreased time spent in active social interaction and the number of rearings and central activity in the social interaction test. It also decreased the number of entries into and the percentage of time spent in open arms and the total number of entries in the elevated plus‐maze. No significant effect was observed in head dipping in the holeboard test, although the number of crossings did increase. These results suggest an anxiogeniclike effect of ketamine in contrast with results previously described for noncompetitive NMDA receptor antagonists. These effects of ketamine are more similar to those described for stimulant drugs such as caffeine, cocaine, or amphetamine in anxiety tests. Depression and Anxiety 5:29–33, 1997.