CNS LEVELS OF MU-OPIOID RECEPTOR (MOR-1) MESSENGER-RNA DURING CHRONIC TREATMENT WITH MORPHINE OR NALTREXONE
CNS LEVELS OF MU-OPIOID RECEPTOR (MOR-1) MESSENGER-RNA DURING CHRONIC TREATMENT WITH MORPHINE OR NALTREXONE
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DOI：
10.1016/0361-9230(95)00079-t
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发表时间：
1995-01-01
影响因子：
3.8
通讯作者：
INTURRISI, CE
中科院分区：
文献类型：
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作者：
BRODSKY, M;ELLIOTT, K;INTURRISI, CE
用溶液杂交法测定长期吗啡或纳曲酮治疗大鼠中枢神经系统中mu阿片受体（MOR-1） mRNA表达水平。吗啡治疗（2 × 75 mg微丸在第1天植入SC，第4天再植入2个）导致对吗啡的抗痛感（镇痛）作用产生耐受性，在治疗第7天通过热板程序进行评估。热板实验后，通过显微解剖获得选定的中枢神经系统区域。感觉运动皮层的pg/mu g RNA中mor1 - mRNA的表达水平为0.7 ~内侧丘脑的15.3。脊髓背角、中缝大核、导水管周围灰质、下丘脑、丘脑内侧或感觉运动皮层的mir -1 mRNA水平未发生变化。在另一项实验中，暴露于纳曲酮（2 × 30 mg颗粒）2天对中枢神经系统的MOR-1 mRNA水平没有影响；然而，暴露8天后，在中缝大核（减少28%）、下丘脑（减少21%）和丘脑内侧（减少27%）检测到减少。长期暴露于吗啡或纳曲酮不会导致大鼠脑全长mir -1 mRNA的数量改变，也不会导致受mir -1核蛋白探针保护的区域（即整个编码区）的大小改变。因此，与吗啡镇痛耐受性发展相关的神经适应过程不涉及MOR-1 mRNA稳态水平的同时变化。慢性纳曲酮治疗似乎会产生区域特异性的mir -1 mRNA水平下调，这可能是继发于纳曲酮诱导的mu受体结合增加。
The CNS levels of mu opioid receptor (MOR-1) mRNA were determined by solution hybridization in rats treated chronically with morphine or naltrexone. Morphine treatment (2 x 75 mg pellets were implanted SC on Day 1 and 2 more on Day 4) resulted in the development of tolerance to morphine's antinociceptive (analgesic) effect, as assessed by the hot plate procedure on treatment Day 7. Following the hot plate test, selected CNS regions were obtained by microdissection. The levels of MOR-1 mRNA in pg/mu g RNA ranged from 0.7 in sensorimotor cortex to 15.3 in medial thalamus. MOR-1 mRNA levels were not altered in the dorsal horn of spinal cord, nucleus raphe magnus, periaqueductal grey, hypothalamus, medial thalamus, or sensorimotor cortex. In a separate experiment, a 2 day exposure to naltrexone (2 x 30 mg pellets) had no effect on CNS levels of MOR-1 mRNA; however, after an 8 day exposure a decrease was detected in the nucleus raphe magnus (by 28%), hypothalamus (by 21%), and medial thalamus (by 27%). Chronic exposure to morphine or naltrexone did not result in alterations in the sire of full-length MOR-1 mRNA from rat brain, or in the size of the region protected by the MOR-1 riboprobe (i.e., the entire coding region). Thus, the neuroadaptive processes associated with the development of analgesic tolerance to morphine do not involve concurrent changes in the steady-state levels of MOR-1 mRNA. Chronic treatment with naltrexone appears to produce a region-specific downregulation of MOR-1 mRNA levels, which may be secondary to the naltrexone-induced increase in mu receptor binding.