TY - JOUR
T1 - Persistent effects of acute stress on fear and drugseeking in a novel model of the comorbidity between post-traumatic stress disorder and addiction
AU - Pizzimenti, Christie L.
AU - Navis, Tom M.
AU - Lattal, K. Matthew
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85027551966&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85027551966&partnerID=8YFLogxK
U2 - 10.1101/lm.044164.116
DO - 10.1101/lm.044164.116
M3 - Article
C2 - 28814468
AN - SCOPUS:85027551966
SN - 1072-0502
VL - 24
SP - 422
EP - 431
JO - Learning and Memory
JF - Learning and Memory
IS - 9
ER -