Even following long periods of abstinence, individuals with anxiety disorders have high rates of relapse to drugs of abuse. Although many current models of relapse demonstrate effects of acute stress on drug-seeking, most of these studies examine stressful experiences that occur in close temporal and physical proximity to the reinstatement test. Here, we assess the effects of a stressful experience in one context on fear and drug-seeking in a different context. We adapt the stress-enhanced fear learning procedure to examine impacts on drug-seeking long after the stressful experience occurred. We find massive footshock in a distinct environment produced an acute increase in corticosterone, long-term hyper-responsivity to a single shock in different contexts with extensive histories of drug-seeking behaviors, enhancements in cocaineinduced conditioned place preference in mice, and persistent enhancements in cue-induced reinstatement of methamphetamine-seeking behavior in rats. Together, these experiments demonstrate that an acute trauma causes persistent changes in responsivity to mild stressors and drug-seeking behavior in other contexts, which mirrors aspects of the comorbidity between post-traumatic stress disorder and substance use disorders. These behavioral approaches provide novel procedures for investigating basic mechanisms underlying this comorbidity and they provide powerful tools for testing preclinical pharmacological and behavioral interventions. [Supplemental material is available for this article.]Compared with the general population, individuals diagnosed with post-traumatic stress disorder (PTSD) have higher rates of substance use disorders (SUDs) (Stewart 1996;McFarlane 1998;Ouimette et al. 1998;Back et al. 2000;Sonne et al. 2003;McCauley et al. 2012;Tipps et al. 2014;Roberts et al. 2015) and are twice as likely to use methamphetamine (METH) than are individuals with trauma exposure that does not lead to PTSD (Smith et al. 2010). Individuals with PTSD are also more likely to relapse to drugs of abuse when cues associated with drug-seeking are encountered, even long after periods of acute stress have ended (Bradizza et al. 2006), suggesting stressors that are temporally and contextually dissociated from drug-seeking may induce longterm changes that contribute to an increased risk for relapse.It has long been observed that stress is a potent inducer of reinstatement (an animal model of relapse) in rodents (e.g., Shaham et al. 2000;Erb et al. 2001;Sanchez and Sorg 2001;Boutrel et al. 2005;Redila and Chavkin 2008;Schindler et al. 2010). Although the ability of stress to induce reinstatement has been well established in the literature, most studies have focused on effects when the organism is tested in a state of acute stress within the drug-seeking context; few studies have evaluated the persistent effects of an acute stressor long after the stress has ended. Individuals with PTSD have traumatic experiences long before relapse and are unlikely to use drugs in the trauma-associated context; avoiding ...
Sensory gating, the ability to suppress sensory information of irrelevant stimuli, is affected in several neuropsychiatric diseases, notably schizophrenia and autism. It is currently unclear how these deficits interact with other hallmark symptoms of these disorders, such as social withdrawal and difficulty with interpersonal relationships. The highly affiliative prairie vole (Microtus ochrogaster) may be an ideal model organism to study the neurobiology underlying social behavior. In this study, we assessed unimodal acoustic sensory gating in male and female prairie voles using the prepulse inhibition (PPI) paradigm, whereby a lower amplitude sound (prepulse) decreases the startle response to a high amplitude sound (pulse) compared to the high amplitude sound alone. Prairie voles showed evidence of PPI at all prepulse levels compared to pulse alone, with both males and females showing similar levels of inhibition. However, unlike what has been reported in other rodent species, prairie voles did not show a within-session decrease in startle response to the pulse alone, nor did they show a decrease in startle response to the pulse over multiple days, highlighting their inability to habituate to startling stimuli (short-and long-term). When contrasted with a cohort of male wildtype C57Bl/6J mice that underwent a comparable PPI protocol, individual voles showed significantly higher trial-by-trial variability as well as longer latency to startle than mice. The benefits and caveats to using prairie voles in future sensory gating experiments are discussed.
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