Enrico P, Mura M A, Esposito G, Serra P, Migheli R, De Natale G, Desole M S, Miele M, Miele E
Institute of Pharmacology, University of Sassari, Viale S. Pietro 43/B, 07100 Sassari, Italy.
Brain Res. 1998 Jun 22;797(1):94-102. doi: 10.1016/s0006-8993(98)00371-0.
Recent findings have shown that systemic morphine increases extracellular dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), ascorbic acid (AA) and uric acid concentrations in the striatum of freely moving rats. The morphine-induced increase in DA oxidative metabolism is highly correlated with that of xanthine. In the present study, we evaluated the effects of subcutaneous (s.c.) naloxone (1 mg/kg) on morphine-induced changes in DA, DOPAC, HVA, 5-hydroxyindoleacetic acid (5-HIAA), AA, uric acid and glutamate in the striatum of freely moving rats using microdialysis. Dialysates were assayed by high performance liquid chromatography with electrochemical detection or (glutamate) ultraviolet detection. Morphine (5-20 mg/kg) given s.c. increased DA, DOPAC+HVA, 5-HIAA, AA and uric acid and decreased glutamate dialysate concentrations over a 3 h period after morphine. Morphine (1 mM), given intrastriatally, did not affect all the above parameters, with the exception of an early short-lasting decrease in AA concentration. Naloxone antagonised all morphine-induced changes with the exception of AA increase and glutamate decrease in dialysate concentrations. Systemic or intrastrial (0.2-2 mM) naloxone increased AA and decreased glutamate dialysate concentrations. When given intranigrally, morphine (1 mM) increased DOPAC+HVA, AA and uric acid and decreased glutamate dialysate concentrations over a 2 h period after morphine; DA and 5-HIAA concentrations were unaffected. These results suggest that: (i) morphine increases striatal DA release and 5-hydroxytryptamine oxidative metabolism by a micro-opioid receptor-mediated mechanism mainly at extranigrostriatal sites; (ii) morphine increases DA and xanthine oxidative metabolism and affects glutamate and AA release by a micro-opioid receptor mediated mechanism acting also at nigral sites; and (iii) a micro-opioid receptor-mediated mechanism tonically controls at striatal sites extracellular AA and glutamate concentrations.
最近的研究结果表明，全身性吗啡会增加自由活动大鼠纹状体中细胞外多巴胺（DA）、二羟基苯乙酸（DOPAC）、高香草酸（HVA）、抗坏血酸（AA）和尿酸的浓度。吗啡诱导的DA氧化代谢增加与黄嘌呤的增加高度相关。在本研究中，我们使用微透析评估了皮下注射（s.c.）纳洛酮（1 mg/kg）对自由活动大鼠纹状体中吗啡诱导的DA、DOPAC、HVA、5-羟色胺乙酸（5-HIAA）、AA、尿酸和谷氨酸变化的影响。通过高效液相色谱-电化学检测或（谷氨酸）紫外检测对透析液进行分析。皮下注射吗啡（5-20 mg/kg）在给药后3小时内增加了DA、DOPAC+HVA、5-HIAA、AA和尿酸，并降低了谷氨酸透析液浓度。纹状体内注射吗啡（1 mM），除了早期短暂降低AA浓度外，并未影响上述所有参数。纳洛酮拮抗了所有吗啡诱导的变化，但透析液中AA增加和谷氨酸降低除外。全身性或纹状体内（0.2-2 mM）纳洛酮增加了AA并降低了谷氨酸透析液浓度。当脑内注射吗啡（1 mM）时，在给药后2小时内增加了DOPAC+HVA、AA和尿酸，并降低了谷氨酸透析液浓度；DA和5-HIAA浓度未受影响。这些结果表明：（i）吗啡主要通过微阿片受体介导的机制在黑质纹状体以外的部位增加纹状体DA释放和5-羟色胺氧化代谢；（ii）吗啡通过微阿片受体介导的机制在黑质部位也起作用，增加DA和黄嘌呤氧化代谢，并影响谷氨酸和AA释放；（iii）微阿片受体介导的机制对纹状体部位细胞外AA和谷氨酸浓度进行紧张性控制。
