阿片机制:涉及神经元动作电位的研究评价

William R. Klemm
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引用次数: 13

摘要

1.1. 从记录神经冲动(动作电位)的研究中可以得出关于阿片类药物对中枢神经系统影响的各种结论。例如,无论是在急性治疗的动物中,还是在对反复接触阿片类药物产生耐受性的发展过程中,阿片类药物作用的种类和特征都存在区域差异。一般来说,阿片类药物抑制神经元活动具有药理立体特异性。兴奋作用(其中一些是立体特异性的,由于去抑制)确实发生在几个大脑区域。在耐受性发育过程中,兴奋效应会变得更加突出。阿片类药物以多种方式与主要神经递质系统相互作用,不仅包括突触后激动剂/拮抗剂现象,还包括突触前和突触后调节功能;这种相互作用的机制了解甚少,是目前许多实验室研究的重点。阿片类药物对不同的大脑结构有深远的影响,这些影响与阿片类药物引起的更突出的行为有关,反映在诸如猝睡、欣快、奖励和镇痛等现象中。然而,目前还没有清晰的认识或统一的理论来解释这些效应是如何产生的。在镇痛的情况下,已知阿片类药物在几个层面上同时作用于伤害性通路:脊髓、脑干和丘脑。对阿片类药物的立体特异性和非立体特异性作用都敏感的细胞的广泛分布使得阿片类药物的各种行为效应可能是通过几种受体类型和神经系统的几个水平介导的。
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Opiate mechanisms: Evaluation of research involving neuronal action potentials

  • 1.

    1. Various conclusions about the opiate effects in the central nervous system can be drawn from studies involving the recording of nerve impulses (action potentials). There are, for example, regional differences in the kind and character of opiate effects, both in acutely treated animals and during the development of tolerance to repeated exposure to opiates.

  • 2.

    2. Generally speaking, opiates depress neuronal activity with pharmacological stereospecificity. Excitatory effects (some of which are stereospecific and due to disinhibition) do occur in several brain regions. Excitatory effects can become more prominent during tolerance development.

  • 3.

    3. Opiates interact with major neurotransmitter systems in a variety of ways that include not only post-synaptic agonist/antagonist phenomena but also pre- and post-synaptic modulatory functions; mechanisms of such interactions are poorly understood and are a focus of current research in many laboratories.

  • 4.

    4. Opiates have profound effects in various brain structures that are known to be associated with the more prominent behaviors that are induced by opiates, as reflected in such phenomena as catalepsy, euphoria, reward and analgesia. There is, however, no clear understanding or unified theory to explain how these effects are produced. In the case of analgesia, the opiates are known to act simultaneously within nociceptive pathways at several levels: spinal, brainstem, and thalamic.

  • 5.

    5. The widespread distribution of cells that are sensitive to both the stereospecific and non-stereospecific effects of opiates makes it likely that the various behavioral effects of opiates are mediated through several receptor types and several levels of the nervous system.

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