Recent studies indicate that the effects of opioid analgesics can be modulated by interactions between opioid as well as nonopioid receptor systems. For example, the N-methyl-D-aspartate (NMDA) receptor system has been shown to be involved in both the acute effects of morphine as well as in the development of morphine tolerance. Although a wealth of studies have examined interactions between opioid and NMDA receptor systems, very little is known about the behavioral mechanisms that underlie these interactions. Therefore, the studies proposed here examine NMDA/opioid interactions in a complex behavioral paradigm, the squirrel money shock titration procedure. This procedure is particularly appropriate for these studies because it provides a way to differentiate the contribution of discriminative and response variables in NMDA/opioid interactions. In addition, studies are proposed to examine pharmacological mechanisms that are important in NMDA/opioid interactions. In particular, investigations will examine NMDA-induced alterations in the effects of opioids that differ from morphine in terms of their relative efficacy. These investigations employ the squirrel monkey titration procedure as well as a rodent tail withdrawal procedure which can be altered so it reveals activity for opioids with low efficacy relative to morphine.
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