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 flow 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 flow 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 microdialysis, 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.