THE NEURAL SEPARABILITY OF OPIOID ANALGESIA & DEPENDENCE

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Focal brain stimulation (FBS) has been used to elicit analgesia in a variety of species, including humans with chronic pain conditions. Brain stimulation-produced analgesia (SPA) shares similarities with the opiate alkaloids, e.g., FBS and morphine-analgesia are naloxone reversible, and SPA delays the development of morphine tolerance. Repetitive FBS of the periaqueductal gray results in some naloxone-elicited signs of opiate withdrawal. Furthermore, FBS of the periaqueductal gray attenuates some opiate withdrawal behaviors in rats undergoing morphine withdrawal. The above evidence suggests that SPA may have a neuronal tie to the phenomena of opioid tolerance and dependence. Other evidence suggests neuronal separation of opiate analgesia from other opioid behaviors, including withdrawal behaviors. Studies using selective opiate receptor blockers have shown a differential ability to block morphone analgesia or the withdrawal signs depending upon the type of receptor being blocked. Researchers have also observed a differential participation of structures within the brain in the components of the morphine withdrawal syndrome. The proposed research investigates whether separation of various opiate behaviors can be demonstrated using focal brain stimulation. The experiments proposed will be conducted in three series: Series I will manipulate the brain stimulation parameters (intensity and duration of FBS) as well as electrode locus and dosage of antagonist in order to determine whether these manipulations elicit differences in the variety or severity of withdrawal behaviors observed. Series II will provide a neuroanatomical map of the substrates involved in FBS-elicited analgesia (short-term stimulation) and withdrawal (long-term stimulation). Series III will use selective opiate receptor blockers in an attempt to prevent specific opiate-like effects of the FBS.