McNally G P, Westbrook R F
School of Psychology, The University of New South Wales, Australia.
Psychopharmacology (Berl). 2000 Mar;149(1):56-62. doi: 10.1007/s002139900337.
Pairings of a sweet taste and injection of morphine result in a learned avoidance of that taste and learned analgesic tolerance. This avoidance is mediated by the drug's peripheral effect, while learned tolerance involves activation of N-methyl-D-aspartate (NMDA) receptors. Exposure to a sweet taste also reduces morphine analgesia. We studied whether this taste-mediated reduction was reversed by an NMDA or peripheral opioid receptor antagonist.
To determine whether an intraoral infusion of saccharin would modulate morphine analgesia in rats, and to study the contribution of NMDA as well as peripheral opioid receptors to this modulation.
Six experiments used the rat's tail-flick response to study the effect of an intraoral infusion of a sodium saccharin solution on morphine analgesia, and the effects of the quaternary opioid receptor antagonist methylnaltrexone as well as the noncompetitive NMDA receptor antagonist MK-801 on this modulation of analgesia.
An intraoral infusion of saccharin reduced the analgesic effects of an intraperitoneal (i.p.) injection of morphine across a range of doses (experiment la), which was not attributable to an influence on tail-skin temperature (experiment 1b). This reduction was mediated by opioid receptors in the periphery and activation of NMDA receptors because morphine analgesia was reinstated by an i.p. injection of either methylnaltrexone (experiment 2a) or MK-801 (experiment 3a), which was not due to the effect of methylnaltrexone (experiment 2b) or MK-801 (experiment 3b) on morphine analgesia in the absence of saccharin.
These results document evidence for an antagonism of morphine analgesia by actions of the drug at peripheral opioid receptors and excitatory amino-acid activity at NMDA receptors. They are discussed with reference to the aversive motivational effects of peripheral opioid receptors and pain facilitatory circuits.
甜味与吗啡注射配对会导致对该味道的习得性回避以及习得性镇痛耐受。这种回避由药物的外周效应介导，而习得性耐受涉及N - 甲基 - D - 天冬氨酸（NMDA）受体的激活。接触甜味也会降低吗啡镇痛效果。我们研究了这种味觉介导的降低是否可被NMDA或外周阿片受体拮抗剂逆转。
确定口腔内输注糖精是否会调节大鼠的吗啡镇痛作用，并研究NMDA以及外周阿片受体对这种调节的作用。
六个实验采用大鼠甩尾反应来研究口腔内输注糖精钠溶液对吗啡镇痛的影响，以及季铵型阿片受体拮抗剂甲基纳曲酮和非竞争性NMDA受体拮抗剂MK - 801对这种镇痛调节的影响。
口腔内输注糖精可降低腹腔注射不同剂量吗啡的镇痛效果（实验1a），这并非归因于对尾皮温度的影响（实验1b）。这种降低由外周阿片受体和NMDA受体的激活介导，因为腹腔注射甲基纳曲酮（实验2a）或MK - 801（实验3a）可恢复吗啡镇痛，这并非由于甲基纳曲酮（实验2b）或MK - 801（实验3b）在无糖精情况下对吗啡镇痛的作用。
这些结果证明了药物在外周阿片受体的作用以及NMDA受体处的兴奋性氨基酸活性对吗啡镇痛具有拮抗作用。结合外周阿片受体的厌恶动机效应和疼痛促进回路对其进行了讨论。
