Exposure to uncontrollable stress alters withdrawal from morphine.

Prior exposure to uncontrollable stress potentiates morphine analgesia. This study was designed to examine the influence of the controllability/uncontrollability of shock as a stressor on the severity of subsequent morphine withdrawal. In Experiment 1, rats that received two daily sessions of 80 yoked-inescapable shocks, in contrast to those given 80 escapable shocks or restrained without shock, showed an enhanced series of correlated withdrawal behaviors (i.e., mouthing, teeth chattering, and head/body shakes) 24 hr later when injected with morphine (5 mg/kg) followed by a naloxone (5 mg/kg) challenge. In Experiment 2, this finding was replicated with escape-yoked-restrained groups of rats given saline injections during the pretreatment phase, but the impact that only inescapable shock had on later precipitated withdrawal was completely blocked when subjects were administered naltrexone (14 mg/kg) before each shock session. These findings are discussed in terms of the capability of inescapable shock to activate an endogenous opiate system(s) and thereby lead to a sensitization of release or receptor processes which could potentiate later morphine withdrawal.