Abstract
Controllable/escapable tailshocks (ESs) do not produce the behavioral and neurochemical outcomes produced by equal yoked uncontrollable/inescapable tailshocks (ISs). The prelimbic cortex is known to play a key role in mediating the protective effects of control. The concepts of act/outcome learning and control seem similar, and act/outcome learning is mediated by a circuit involving the prelimbic cortex and posterior dorsomedial striatum (DMS). Thus, we tested the involvement of the DMS in the protective effect of ES, in rats. First, we examined Fos immunoreactivity in both the DMS and dorsolateral striatum (DLS) after ES and yoked IS. We then investigated the effect of blocking DMS or DLS N-methyl-d-aspartate receptors with the specific antagonist D-(-)-2-amino-5-phosphopentanoic acid (D-AP5) on the release of dorsal raphe nucleus serotonin (5-HT) during ES, as well as on the level of anxiety produced by the ES experience 24 h later. ES, but not yoked IS, produced a large increase of Fos activity in the DMS. Consistent with the Fos data, D-AP5 in the DMS, but not in the DLS, prevented the inhibition of dorsal raphe nucleus 5-HT release normally produced by ES. Furthermore, D-AP5 administered into the DMS before ES, but not into the DLS, increased anxiety 24 h later, leading to levels similar to those produced by IS. These results suggest that, as with appetitive act/outcome contingency learning, the protective effects of behavioral control over a stressor require the DMS.