THE NEURAL SEPARABILITY OF OPIOID ANALGESIA & DEPENDENCE

局灶性脑刺激(FBS)已被用来诱导一种 种类繁多，包括患有慢性疼痛的人类。脑区 刺激产生的镇痛(SPA)与阿片类药物有相似之处 生物碱，如FBS和吗啡止痛是可逆的，并且 SpA延缓了吗啡耐受性的发展。重复的FBS 中脑导水管周围灰质导致纳洛酮引起的一些阿片剂征象 戒烟。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类戒断行为。这个 上述证据表明，SPA可能与这些现象有神经元联系 阿片类药物的耐受性和依赖性。 其他证据表明阿片类镇痛剂的神经元分离。 阿片类行为，包括戒断行为。研究使用选择性 阿片受体阻滞剂已经显示出不同的阻断能力 吗啡止痛或戒断体征取决于类型 感受器被阻断。研究人员还观察到了一种差异 脑内结构在脑内各成分中的参与 吗啡戒断综合症。 这项拟议的研究调查了各种鸦片类药物的分离 行为可以通过局部大脑刺激来展示。这个 拟议的实验将分三个系列进行：系列I将 操纵脑刺激参数(FBS的强度和持续时间) 以及电极轨迹和拮抗剂用量，以确定 这些操作是否会导致多样性或严重性的差异 观察到的戒断行为。第二系列将提供一个神经解剖学 FBS镇痛相关底物图(短期) 刺激)和戒断(长期刺激)。系列III将使用 选择性阿片受体阻滞剂试图预防特定的 FBS的鸦片样效应。

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.