THE NEURAL SEPARABILITY OF OPIOID ANALGESIA & DEPENDENCE

局灶性脑刺激（FBS）已被用于引起镇痛， 各种物种，包括患有慢性疼痛病症的人类。 大脑 刺激产生的镇痛（SPA）与阿片类药物相似 生物碱，例如，FBS和吗啡镇痛是纳洛酮可逆的， SPA延缓吗啡耐受的发展。 的重复FBS 中脑导水管周围灰质导致一些纳洛酮引起的阿片样物质体征 戒断 此外，中脑导水管周围灰质的FBS减弱了一些 吗啡戒断大鼠的阿片戒断行为。 的 上述证据表明，SPA可能与这种现象有神经联系 阿片类药物的耐受性和依赖性 其他证据表明，阿片类镇痛与其他神经元分离。 阿片类药物行为，包括戒断行为。 使用选择性 阿片受体阻滞剂显示出不同的阻滞能力， 吗啡酮镇痛或戒断症状取决于 受体被阻断。 研究人员还观察到， 脑内结构参与脑的组成部分， 吗啡戒断综合征 本研究旨在探讨不同阿片类药物的分离是否 行为可以通过局部脑刺激来证明。 的 建议的实验将在三个系列进行：系列I将 操纵脑刺激参数（FBS的强度和持续时间） 以及电极位置和拮抗剂的剂量，以确定 这些操作是否会引起品种或严重程度的差异， 观察到的戒断行为 系列II将提供神经解剖学 FBS引起的镇痛（短期）中涉及的底物图 刺激）和撤回（长期刺激）。 系列三将使用 选择性阿片受体阻滞剂，试图防止特定的 FBS的阿片样作用。

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.