急性可卡因注射对新生仔猪脑内多巴胺、血流量和氧压的影响

Yonetani M., Huang C.C., Lajevardi N., Pastuszko A., Delivoriapapadopoulous M., Anday E.
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引用次数: 8

摘要

本研究检测了急性可卡因给药对新生仔猪皮层血管中氧压的影响,以及对纹状体中血氧和细胞外多巴胺水平的影响。磷光的氧依赖性猝灭被用来连续监测皮层血管中的氧压。急性可卡因注射(1.5 mg/kg iv)后,皮质氧压从36.3±1.2迅速下降到32.9±1.4 Torr,并在注射后120min内保持在较低水平。激光多普勒测定,注射可卡因后5分钟纹状体血浓度下降8-10%。这种血流减少在注射后40分钟具有统计学意义。细胞外多巴胺,用体内微透析测量,显示可卡因注射后大量增加。多巴胺水平在给药后15 min由14±7 pmol/ml上升至88±21 pmol/ml,然后降至45±11 pmol/ml,并在给药后120 min保持稳定。细胞外多巴胺水平升高的机制可能包括可卡因对多巴胺转运体的直接作用和/或由于脑氧合和血流量减少而产生的间接作用。细胞外多巴胺的增加可能导致神经元代谢的一些改变,对神经元功能有潜在的有害影响。
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Effect of Acute Cocaine Injection on the Extracellular Level of Dopamine, Blood Flow, and Oxygen Pressure in Brain of Newborn Piglets

The present study examined the effects of acute cocaine administration on oxygen pressure in the vasculature of the cortex as well as on blood dow and extracellular levels of dopamine in the striatum of newborn piglets. The oxygen dependent quenching of phosphorescence was used to continuously monitor oxygen pressure in the vasculature of the cortex. Following acute cocaine injection (1.5 mg/kg iv) the cortical oxygen pressure rapidly decreased from 36.3 ± 1.2 to 32.9 ± 1.4 Torr and remained at the lower level during the 120 min of postinjection period during which measurements were made. Blood dow in striatum, as determined by laser Doppler, was decreased by 8-10% at 5 min after injection of cocaine. This decrease in blood flow was statistically significant up to 40 min postinjection. Extracellular dopamine, measured using in vivo micro dialysis, showed a large increase after cocaine injection. The dopamine level increased from 14 ± 7 to 88 ± 21 pmol/ml by 15 min after drug administration, then decreased to 45 ± 11 pmol/ml and remained stable for the 120 min post-injection period. The mechanism(s) by which the increase in the extracellular level of dopamine occurred may include a direct effect of cocaine on the dopamine transporter and/or an indirect effect due to the decrease in cerebral oxygenation and blood flow. The increase in extracellular dopamine can be responsible for several alterations in neuronal metabolism with potentially deleterious effects on neuronal function.

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