SummaryAdvances in medical technology have increased the number of individuals who survive cardiac arrest/ cardiopulmonary resuscitation (CPR). This increased incidence of survival has created a population of patients with behavioral and physiologic impairments. We used temperature manipulations to characterize the contribution of central nervous system damage to behavioral deficits elicited by 8 minutes of cardiac arrest/CPR in a mouse model. Once sensorimotor deficits were resolved, we examined anxiety-like behavior with the elevated plus maze and social interaction with an ovariectomized female. We hypothesized that anxiety-like behavior would increase and social interaction would decrease in mice subjected to cardiac arrest/CPR and that these changes would be attributable to central nervous system damage rather than damage to peripheral organs or changes orchestrated by the administration of epinephrine. Mice that were subjected to cardiac arrest/CPR while the peripheral organs, but not the brain, were protected by hypothermia exhibited increased anxiety-like behavior and decreased social interaction, whereas mice with hypothermic brains and peripheral organs during cardiac arrest/CPR did not exhibit behavioral impairments. The present study demonstrates that central nervous system damage from cardiac arrest/CPR results in increased anxiety and decreased social interaction and that these behavioral changes are not attributed to underlying sensorimotor deficits, dynamics of arrest and CPR, or peripheral organ damage. KeywordsCardiac arrest; Cardiopulmonary resuscitation; Glucocorticoids; Sudden death; Anxiety; Social interaction Cardiac arrest/cardiopulmonary resuscitation (CPR) results in one death every minute in the United States and approximately 250,000 deaths per year (American Heart Association, 2002). Increased public awareness of symptoms and advances in medical technology have increased the number of individuals who survive cardiac arrest/CPR through early Address correspondence to Gretchen N. Neigh, Department of Psychology, Townshend Hall, 1885 Neil Avenue Mall, Ohio State University, Columbus, OH 43210; e-mail:neigh.1@osu.edu.. Supported by National Institutes of Health Grants NS 40267 and NS20020 and American Heart Association EIA (A.C.D.). Also supported by grants J1864-MED and J2106 from the Austrian Science Fund (Fond zur Förderung der Wissenschaftlichen Forschung) (J. Kofler). (Bunch et al., 2003; Hypothermia After Cardiac Arrest Study Group, 2002;Paradis et al., 2002). The increased incidence of survival presents a class of physiologic and behavioral deficits that are related to the anoxic/hypoxic state experienced during cardiac arrest/CPR (de Vos et al., 1999;Drysdale et al., 2000;Pusswald et al., 2000). Several laboratories have examined the molecular and cellular effects of cardiac arrest/CPR (Bottiger et al., 1999;Katz et al., 2001;Sadowski et al., 2002), but until recently, little was known about behavioral deficits in cardiac arrest/CPR survivors. NIH Public AccessThe effect of su...