TY - JOUR
T1 - Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma
AU - Pennington, Zachary T.
AU - Trott, Jeremy M.
AU - Rajbhandari, Abha K.
AU - Li, Kevin
AU - Walwyn, Wendy M.
AU - Evans, Christopher J.
AU - Fanselow, Michael S.
N1 - Funding Information:
This work was supported by NIDA DA005010, NIMH RO1 MH115678, NIMH F31 MH108257-02, and NIDA 5T32DA007135. MSF serves as director of research for Neurovation Labs. ZTP, JMT, AKR, KL, WMW and CE have no financial disclosures to report.
Publisher Copyright:
© 2019, The Author(s).
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Despite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries.
AB - Despite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries.
UR - http://www.scopus.com/inward/record.url?scp=85076159568&partnerID=8YFLogxK
U2 - 10.1038/s41386-019-0559-5
DO - 10.1038/s41386-019-0559-5
M3 - Article
C2 - 31787748
AN - SCOPUS:85076159568
SN - 0893-133X
VL - 45
SP - 482
EP - 490
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 3
ER -