Stress can increase or decrease anxiety depending on the timing of the stressor

The purpose of these experiments was to determine the immediate and delayed effects of stress on anxiety/depressive behavior. For the open field and elevated plus maze experiments male CD1 mice (Charles River) were used (n=6-8 per group; arrived at 7 weeks of age, tested at 9-11 weeks, handled for 5 days prior to testing). The GFAP-tk mice used for the novelty-suppressed feeding test were as described in Snyder, 2011, Nature. Mice were housed 4/cage, kept on a 12 hour light/dark cycle with lights on at 6 am and were tested during the light phase. Testing was performed either directly from the home cage (controls), immediately following 30 min restraint (stress) or following 30 min restraint with a 30 min post-restraint delay interval (stress+delay).

Figure 1: Increased fear/anxiety in the open field immediately following stress. a) The open field was a white plastic box (50cm x 50cm x 50cm) which was divided into outer (o), middle (m), and center (c) regions. Mice were tracked with Ethovision software (Noldus) and latency to approach the center region and time spent in the 3 regions during a 15 min test was calculated. Light intensity was approximately 150 lux. b) The presence of an object (~2 cm diameter, 3 cm tall wire metal cylinder containing a marble) in the center of the open field increased time spent in this subregion, and was therefore included in subsequent experiments (i.e. d-h; ****t-test P

Figure 2: Reduced fear/anxiety in the elevated plus maze 30 min after stress. Mice were subjected to a 5 min test in the EPM under bright (~150 lux; a-g) and dark (15 lux; h-n) conditions. The EPM had two open arms and two opaque closed arms and was located in the center of the testing room. a) Stress+delay increased the amount of time spent in the open arm during the first 2.5 min of the test (bin 1; *t-test, P

In sum, stress can increase anxiety immediately after termination of the stressor: stressed mice spent less time than controls in the center of the open field. Stress can also reduce anxiety at later times after termination of the stressor: stress+delay mice spent more time in the open arms of the elevated plus maze, stress+delay mice displayed more head dipping behavior in the elevated plus maze, and stress+delay mice ate sooner in the novelty- suppressed feeding test. Also, in the open field, 1/3 of mice in the control and stress groups did not approach the center until 4+ min had elapsed. In contrast, though not significantly different, there was less variability in the stress+delay mice with all approaching the center by ~2 min, consistent with the possibility that stress+delay is reducing anxiety in some of these mice.