急性和慢性吗啡治疗以及吗啡戒断对大鼠活体脑的影响。

The effects of acute and chronic morphine treatment and of morphine withdrawal on rat brain in vivo.

作者信息

Miller A L, Hawkins R A, Harris R L, Veech R L

出版信息

Biochem J. 1972 Sep;129(2):463-9. doi: 10.1042/bj1290463.

DOI:10.1042/bj1290463

PMID:4674603

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1174096/

Abstract

The effects of morphine, nalorphine, acetazolamide, and 10% CO(2) on brain metabolite concentrations of 24h-starved rats were studied. 2. A single dose of morphine (20mg/kg body wt.) caused an increase in brain glucose concentration (42%) and decreased concentrations of lactate (24%), pyruvate (29%), citrate (20%), alpha-oxoglutarate (16%), malate (14%) and creatine phosphate (10%) after 30min. No changes were found in adenine nucleotide concentrations. 3. The same dose of morphine increased arterial CO(2) from 5.07 to 7.60 kN/m(2) (38 to 57 Torr), decreased the pH from 7.41 to 7.31 and decreased O(2) from 14.1 to 10.8kN/m(2) (106 to 81 Torr) at 30min. 4. Rats injected with morphine three times daily (20mg/kg body wt.) for 2 weeks had no changes in brain metabolite concentrations or in blood gases 30min after their last injection. 5. Nalorphine (an antagonist of morphine) caused essentially no changes in brain metabolite concentrations in normal rats. When nalorphine (20mg/kg) was administered to rats previously treated with morphine three times daily for 2 weeks, there was an increase in brain glucose (100%), lactate (23%), pyruvate (18%) and citrate (10%) concentrations. 6. Acetazolamide (an inhibitor of carbonic anhydrase) and 10% CO(2) increased the arterial CO(2) from 4.79 to 6.78kN/m(2) (36 to 51 Torr) and from 5.32 to 10.8kN/m(2) (40 to 81 Torr) respectively. 7. Both acetazolamide and 10% CO(2) caused changes in brain metabolite concentrations similar to those for acutely administered morphine. Thus 10% CO(2) caused increased brain glucose concentration (123%) and decreased brain lactate (46%), pyruvate (34%), citrate (26%), alpha-oxoglutarate (33%), malate (45%) and creatine phosphate (7%) concentrations. No changes in adenine nucleotide concentrations were found. 8. The results indicate that the effect of morphine on brain metabolite concentrations may be accounted for by the increased [CO(2)]. 9. These findings constitute a consistent pattern of metabolic changes after acute morphine administration, morphine addiction, and withdrawal from morphine addiction.

摘要

研究了吗啡、烯丙吗啡、乙酰唑胺和10%二氧化碳对饥饿24小时大鼠脑代谢物浓度的影响。2. 单次注射吗啡（20mg/kg体重）30分钟后，脑葡萄糖浓度升高（42%），乳酸（24%）、丙酮酸（29%）、柠檬酸（20%）、α-酮戊二酸（16%）、苹果酸（14%）和磷酸肌酸（10%）浓度降低。腺嘌呤核苷酸浓度未发现变化。3. 相同剂量的吗啡在30分钟时使动脉二氧化碳分压从5.07kN/m²（38 Torr）升至7.60kN/m²（57 Torr），pH从7.41降至7.31，氧分压从14.1kN/m²（106 Torr）降至10.8kN/m²（81 Torr）。4. 每天注射三次吗啡（20mg/kg体重），持续2周的大鼠在最后一次注射后30分钟，脑代谢物浓度和血气均无变化。5. 烯丙吗啡（吗啡拮抗剂）对正常大鼠脑代谢物浓度基本无影响。当给先前每天注射三次吗啡，持续2周的大鼠注射烯丙吗啡（20mg/kg）时，脑葡萄糖（100%）、乳酸（23%）、丙酮酸（18%）和柠檬酸（10%）浓度升高。6. 乙酰唑胺（碳酸酐酶抑制剂）和10%二氧化碳分别使动脉二氧化碳分压从4.79kN/m²（36 Torr）升至6.78kN/m²（51 Torr）和从5.32kN/m²（40 Torr）升至10.8kN/m²（81 Torr）。7. 乙酰唑胺和10%二氧化碳引起的脑代谢物浓度变化与急性注射吗啡相似。因此，10%二氧化碳使脑葡萄糖浓度升高（123%），脑乳酸（46%）、丙酮酸（34%）、柠檬酸（26%）、α-酮戊二酸（33%）、苹果酸（45%）和磷酸肌酸（7%）浓度降低。腺嘌呤核苷酸浓度未发现变化。8. 结果表明，吗啡对脑代谢物浓度的影响可能是由[二氧化碳]升高所致。9. 这些发现构成了急性注射吗啡、吗啡成瘾及吗啡成瘾戒断后代谢变化的一致模式。