Conditioned fear exacerbates acute morphine dependence

A variety of physical stressors have been shown to enhance reactivity to opioid drugs. Few studies have examined the effects of nonphysical stressors on opioid drug reactivity. In this regard, it has previously been shown that animals administered morphine in the presence of shock-associated cues demonstrate increases in hypoalgesia relative to nonshock control animals. These findings have typically been viewed as being mediated by the activation of endogenous pain inhibition systems via conditioned fear. In this series, we further examined the nature of these effects by assessing the effects of conditioned fear on acute morphine dependence. Experiment 1 revealed that animals administered 3 mg/kg morphine in the presence of context fear cues demonstrated an enhanced withdrawal response when removed and administered 3 mg/kg naloxone. Because it is known that conditioning effects do not diminish over time, a second experiment examined whether the enhancement of acute dependence by context fear would still be evident 72 h postconditioning. As in Experiment 1, animals administered morphine in a context associated with shock demonstrated an enhancement of acute dependence. Experiment 2b revealed that the shock parameters used in these studies can induce a hypoalgesic response on the test that is opioid mediated. These findings are discussed with regard to the neuroanatomy of fear systems as they relate to the neuropharmacological study of opioid withdrawal.