Anxiogenic effects of brief swim stress are sensitive to stress history

Abstract

Stressors that are controllable not only protect an individual from the acute consequences of the stressor, but also the consequences of stressors that occur later. This phenomenon, termed “behavioral immunization”, is studied in the rat by first administering tailshocks each of which can be terminated (escapable tailshock) by an instrumental wheel-turn response prior to exposure to a second stressor. Previous research has shown that exposure to escapable tailshock blocks the neurochemical and behavioral consequences of later inescapable tailshock or social defeat stress. Here we explored the generality of behavioral immunization by examining the impact of prior escapable tailshock on the behavioral consequences of cold swim stress. Exposure to a 5 min cold-water (19 °C) swim caused an anxiety-like reduction in social interaction that was dependent upon 5-HT_2C receptor activation. Rats with prior exposure to escapable tailshock did not develop the swim-induced anxiety. Plasticity in the medial prefrontal cortex, a hypothetical neural mechanism underlying behavioral immunization, is discussed.

Introduction

There is enormous variability in how individuals respond to stressors and whether the stressor episode will interact with the development of psychiatric disorders (Alleva and Francia, 2009, Dudley et al., 2011, Franklin et al., 2012). Although it is clear that stress history is an important modulating factor, the features of prior experience that are critical remain largely unknown. Often, prior exposure to a stressor or adverse circumstance increases the behavioral or neurochemical impact of a subsequent stressor, particularly if the prior stressor is intense and different from the later target stressor (Girotti et al., 2011, Johnson et al., 2002, Pelton et al., 1997). Until recently, the emphasis has been on attempting to determine the mechanisms by which prior experiences produce such potentiation. However, there are circumstances under which prior stress experience blunts the impact of subsequent stressors (Lyons and Macri, 2011), and there has been an increasing interest in understanding the processes that underlie “resilience” (Dudley et al., 2011, Russo et al., 2012, Southwick and Charney, 2012).

The degree of behavioral control that the organism is able to exert over the stressor is arguably the most potent experiential aspect of the stressor episode that modulates its influence on behavioral and neurochemical reactions to subsequent stressors (Cabib et al., 2012, Southwick and Charney, 2012, Southwick et al., 2005). The presence of behavioral control (the ability to alter the duration, intensity, temporal pattern, etc. of an adverse event by means of behavioral responses) not only blunts the impact of the stressor being experienced, but also potently reduces the behavioral impact of subsequent uncontrollable stressors. Exposure to intense stressors, such as social defeat or inescapable tailshocks, produces a constellation of behavioral changes that include both anxiety-like (e.g., reduced social investigation) and depressive-like (e.g., anhedonia) elements (Maier and Watkins, 2005, Overstreet, 2012). These behavioral effects are mediated, at least in part, by changes in dorsal raphe nucleus (DRN) 5-HT neurons that are consequent to the intense activation of these neurons produced by the stressor (for review see Maier and Watkins, 2005). Experience with a series of escapable tailshocks (ES) during which each tailshock can be terminated by turning a small wheel located in the front of the chamber, blocks both the anxiety and depression-like behavioral changes, as well as the 5-HT DRN activation produced by later inescapable tailshock (Amat et al., 2006), a phenomenon that has been called “behavioral immunization” (Williams and Maier, 1977). An initial experience with exactly matched inescapable tailshocks (IS) does not produce immunization, so the immunization depends on the controllability of the initial tailshocks. Strikingly, the immunizing effects of ES persist for at least 7 days, and may persist for at least a month, depending on the outcome measure (Kubala et al., 2012, Rozeske et al., 2012).

Because mechanisms of stress resistance and resilience are critically important to understanding the development of psychiatric disease (Russo et al., 2012), our laboratory has sought to identify the procedural limits of the behavioral immunization phenomenon. Although the work cited above involved administration of tailshock in different environments in the two phases of the procedure, the stressors were fundamentally the same. A critical issue with regard to the immunization phenomenon concerns whether control over tailshock would afford protection against qualitatively different stressors. At present, only one experiment has been directed at this issue. Amat et al. (2010) exposed rats to social defeat 7 days after ES or IS. As above, prior ES prevented the activation of the DRN and the anxiety-like behavioral changes associated with social defeat. This finding suggests a fundamental organismic change produced by an experience with control over tailshock and here we explore the generality of this trans-stressor effect by determining whether ES would blunt the changes produced by acute swim exposure. Because our interests focus on the consequences of stressor exposure on anxiety-like behavior, we first determined whether forced swim would induce social avoidance. In the first experiment the rats were exposed to a 5 minute swim in cold 19 °C water and tested for social exploration 1 h after swim. In the second experiment the rats have received either ES, IS or no stress 7 days before the forced swim and social exploration tests. Finally, to determine if forced swim-induced anxiety depends on 5-HT_2C receptors, a critical mediator of anxiety in this test (Christianson et al., 2010), the rats were given the 5-HT_2C receptor antagonist SB242084 after the swim.