Poppies and PTSD: Opioid influence on a preclinical model of posttraumatic stress disorder

Posttraumatic Stress Disorder (PTSD) is an anxiety disorder that affects over 7.7 million adults and carries an estimated societal cost of ;Mu opioid receptor (MOR) analgesics, such as morphine, are often given as a response to trauma, and there is emerging evidence that they are, at least partially, protective against PTSD. The kappa opioid receptor (KOR) system has also been implicated in stress-related processes, with KOR agonists reported to enhance stress in both laboratory animals and in humans, and KOR antagonists reported to attenuate stress-like behaviors preclinically. This project attempted to clarify part of the role of the mu and kappa opiate receptor systems in mediating effects of Pavlovian fear conditioning in mice as a predictor of their involvement in some of the signs and symptoms of PTSD.;Kappa agonists increased acute fear responses but surprisingly also facilitated fear extinction learning. This would suggest that the use of kappa agonists might increase the efficiency and effectiveness of this therapy and could improve existing PTSD patient outcomes. MOR agonists, as well as KOR antagonists reduced acute and long-term fear behavior. These results support that the use KOR analgesics like morphine and fentanyl in the treatment of trauma could have an added benefit of reducing the emergence and persistence of PTSD. Self-medication may help explain the comorbidity of opioid abuse in PTSD patient populations. Understanding the relative effects of these opiate ligands could lead to more informed usage of MOR analgesics which vary in mu and kappa receptor activity under battlefield and other traumatic conditions.