Long-lasting marked inhibition of periaqueductal gray-evoked defensive behaviors in inescapably-shocked rats.

Clinical evidence suggests that depression and trauma predispose the subject to panic. Accordingly, here we examined the late effects of uncontrollable stress, a presumptive model of depression and/or traumatic disorder, on panic-like behaviors evoked by electrical stimulation of the dorsal periaqueductal gray (DPAG). Changes in anxiety and depression were also assessed in the elevated plus-maze (EPM) and forced-swimming test (FST), respectively. Rats with electrodes in the DPAG were subjected to a 7-day shuttle-box one-way escape yoked training with foot-shocks either escapable (ES) or inescapable (IS). The day after the end of one-way escape training, rats were trained in a two-way escape novel task (test-session) to ascertain the effectiveness of uncontrollable stress. DPAG stimulations were carried out in an open field, both before the escape training and 2 and 7 days after it, and EPM and FST were performed on the 8th and 10th days afterwards, respectively. Controls were either trained with fictive shocks (FS) or subjected to intracranial stimulations only. Although the ES rats performed significantly better than the IS group in the two-way escape task, groups did not differ with respect to either the anxiety or depression scores. Unexpectedly, however, IS rats showed a marked attenuation of DPAG-evoked freezing and flight behaviors relative to both the ES and FS groups, 2 and 7 days after one-way escape training. The conjoint inhibition of passive (freezing) and active (flight) defensive behaviors suggests that IS inhibits a DPAG in-built motivational system that may be implicated in depressed patients' difficulties in coping with daily-life stress.