Intermittent dosing prolongs tolerance to the antinociceptive effect of morphine microinjection into the periaqueductal gray.
Intermittent dosing prolongs tolerance to the antinociceptive effect of morphine microinjection into the periaqueductal gray.
复制标题
间歇给药可延长导水管周围灰质微注射吗啡抗伤害作用的耐受性。
DOI：
10.1016/j.brainres.2005.08.024
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发表时间：
2005
期刊：
影响因子：
2.9
通讯作者：
Ingram,SusanL
中科院分区：
文献类型：
--
作者：
Morgan,MichaelM;Tierney,BradleyW;Ingram,SusanL
耐受性的抗伤害性效应的微量注射吗啡到腹外侧的中脑导水管周围灰质（vPAG）的发展与重复管理。本实验的目的是确定耐受性的幅度和持续时间是否因注射间隔而异。将吗啡或生理盐水注射到大鼠的vPAG中，每天一次，持续4天，或每天两次，持续2天。所有大鼠均在第五次注射时将吗啡注射到vPAG中，以确定是否产生了耐受性。吗啡微量注射在两个吗啡预处理组中产生耐受性，无论剂量间隔如何。一周和两周后，微量注射吗啡产生增加热板潜伏期在所有组中，除了大鼠每天微量注射吗啡预处理。也就是说，耐受性是明显的2周后，诱导耐受性产生的每日注射吗啡，但不是每天两次。虽然已显示较长的给药间隔可延长全身性吗啡给药后的耐受持续时间，但这是首次报告显示与直接向脑内给予吗啡具有类似的效果。鉴于联想学习的基础与全身吗啡给药的耐受性延长，目前的数据表明，关联机制的耐受性也从事吗啡给药时，仅限于PAG。
Tolerance to the antinociceptive effect of microinjecting morphine into the ventrolateral periaqueductal gray (vPAG) develops with repeated administration. The objective of the present experiment was to determine whether the magnitude and duration of tolerance differ depending on the interval between injections. Rats were injected with morphine or saline into the vPAG either once daily for 4 days or twice daily for 2 days. All rats were injected with morphine into the vPAG for the fifth injection to determine whether tolerance had developed. Morphine microinjection produced tolerance in both morphine-pretreated groups regardless of inter-dose interval. One and two weeks later, microinjection of morphine produced an increase in hot plate latency in all groups except rats pretreated with daily morphine microinjections. That is, tolerance was evident 2 weeks following the induction of tolerance produced by daily, but not twice daily injections of morphine. Although a long inter-dose interval has been shown to prolong the duration of tolerance after systemic morphine administration, this is the first report showing a similar effect with direct administration of morphine into the brain. Given that associative learning underlies prolonged tolerance with systemic morphine administration, the present data suggest that associative mechanisms of tolerance are also engaged when morphine administration is restricted to the PAG.