Altered ligand binding of D1 and D2 dopamine receptors in response to hypoxia and posthypoxic reoxygenation.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
A Pastuszko
Publications and source records attributed to A Pastuszko.
Regional expression of heat shock protein 72 mRNA following mild and severe hypoxia in neonatal piglet brain.
The present study examined the effect of hypoxia on expression of 72-kDa heat shock protein (hsp72) mRNA in the newborn brain. The studies were carried out in anesthetized and mechanically ventilated newborn piglets, age 3-5 days. Hypoxic insult was induced by decreasing the fraction of inspired oxygen (FiO2) from 21% to 6% or 10% for 1 h. Oxygen pressure in the microvasculature of the cortex (cortical pO2) was measured by oxygen dependent quenching of the phosphorescence of phosphor dissolved in blood. Following the two hours of normoxic recovery, regional expression of the 72-kDa heat shock protein (hsp72) mRNA was determined using in situ hybridization and autoradiography. Two grades of hypoxia were studied. Mild hypoxia (cortical pO2 = 10-30 mm Hg) induced the expression of hsp72 mRNA predominantly in the subcortical white matter. In individual animals of this group, the extent of expression varied from isolated regions to widespread involvement of the white matter. Severe hypoxia (cortical pO2 = 3-10 mm Hg) induced the expression of hsp72 mRNA in both white and gray matter regions, with strong expression occurring in the cerebral cortex of individual animals. The present results indicate that immature white matter is more sensitive than gray matter to the hypoxia induced expression of hsp72 mRNA. Further, increased expression of hsp72 mRNA may be an indicator of a pathologic degree of hypoxic stress, and the observed increase may indicate that in the newborn brain the immature white matter is particularly sensitive to injury by hypoxia-ischemia and reperfusion.
Animals↗
Effect of hemorrhagic hypotension on hydroxyl radicals in cat brain.
This study investigated the relationships between blood pressure, cortical oxygen pressure and hydroxyl radicals in the brain of adult cats during hemorrhagic hypotension and retransfusion. Oxygen pressure in the blood of the cortex was measured optically by the oxygen dependent quenching of phosphorescence and hydroxyl radicals by in vivo microdialysis. Following a 2 h stabilization period after implantation of the microdialysis probe in the striatum, the mean arterial blood pressure (MAP) was decreased in a stepwise manner from 132 +/- 2 Torr (control) to 90 +/- 1 Torr, 70 +/- 3 Torr and 50 +/- 3 Torr, holding the pressure at each level for 15 min. The whole blood was then retransfused and measurements were continued for 90 min. Cortical oxygen pressure progressively decreased with decrease in MAP, decreasing from 50 +/- 2 Torr (control) to 42 +/- 1 Torr, 31 +/- 2 Torr and 22 +/- 2 Torr, respectively. The level of hydroxyl radical increased by 20-25% following first 15 min of bleeding and stay on this level during the remaining period of hypotension. Maximal increase (by 78%) in level of hydroxyl radicals was observed after 15 min of retransfusion. The present study demonstrated that during hypotension and retransfusion there was an increase in the level of hydroxyl radicals in striatum. These can be important mediators of postischemic injury to the striatum.
Animals↗
Excitatory amino acid receptor antagonists decrease hypoxia induced increase in extracellular dopamine in striatum of newborn piglets.
The present study tested the hypothesis that the increase in extracellular striatal dopamine during hypoxia is least partly associated with activation of N-methyl-D-aspartate (NMDA) and/or non-NMDA excitatory amino acid receptors. Studies were performed in anesthetized and mechanically ventilated 2-3 days old piglets. Hypoxic insult was induced by decreasing the oxygen fraction in inspired gas (FiO2) from 22 to 7% for 1 h, followed by 1 h reoxygenation at 22%. Cortical oxygen pressure was measured optically by oxygen dependent quenching of phosphorescence, and extracellular striatal dopamine was measured using in vivo microdialysis. The microdialysis probes were perfused with Ringer solution +/- 50 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) or 50 microM 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). One hour of hypoxia decreased the cortical oxygen pressure from 46 +/- 3 Torr to 10 +/- 1.8 Torr. In striatum perfused with Ringer, statistically significant increase in extracellular dopamine, to 1050 +/- 310% of control, was observed after 20 min of hypoxia. By 40 min of hypoxia the extracellular level of dopamine increased to 4730 +/- 900% of control; by the end of the hypoxic period the values increased to 18,451 +/- 1670% of control. The presence of MK-801 in the perfusate significantly decreased the levels of extracellular dopamine during hypoxia. At 20, 40 and 60 min of hypoxia extracellular level of dopamine increased to 278 +/- 94% of control, 1530 +/- 339% of control and 14,709 +/- 1095 of control, respectively. The presence of NBQX caused a statistically significant decrease, by about 30%, in the extracellular dopamine compared to control, only at the end of the hypoxic period. It can be concluded that in striatum of newborn piglets, the excitatory NMDA receptors but not the non-NMDA receptors may be modulating the changes in extracellular levels of dopamine. The NMDA receptor antagonist, MK-801, may exert part of its reported neuroprotective effect to hypoxic stress in striatum by decreasing the levels of extracellular dopamine.
Animals↗
Response of cortical oxygen and striatal dopamine in newborn piglets to alcohol infusion under normoxic and hypoxic conditions.
Explore the source record for details and available documents.
Animals↗
Response of cortical oxygen and striatal extracellular dopamine to metabolic acidosis in newborn piglets.
This study determined the relationships of metabolic acidosis, cortical oxygen pressure, and striatal extracellular dopamine in the brain of newborn piglets. After a baseline period of 120 minutes, a 0.6 N HCl solution was infused intravenously to decrease the blood pH to about 7.0-7.05. The metabolic acidosis was then corrected by injecting sodium bicarbonate and measurements were continued for one hour. The results show that decreased blood pH to about 7.2-7.15 does not cause a statistically significant change in mean blood pressure, cortical oxygen pressure or striatal extracellular dopamine. Further decrease in pH caused significant decrease in both blood pressure and cortical oxygen pressure. By the end of the period of acidosis the cortical oxygen pressure decreased from the control value of 43 +/- 4 Torr to 22 +/- 8 Torr. Changes in the extracellular level of striatal dopamine were parallel to changes in cortical oxygen pressure. The extracellular dopamine increased to 1270% of the control on the end of HCl injection. Infusion of bicarbonate to correct the acidosis resulted in an increase of cortical oxygen and progressive decline of dopamine in the extracellular medium. It is suggested that the level of extracellular dopamine in the striatum of newborn piglets was not directly affected by decrease in pH but was dependent on changes in tissue oxygen pressure during metabolic acidosis.
Acidosis↗
Effect of hemorrhagic hypotension on cortical oxygen pressure and striatal extracellular dopamine in cat brain.
This study investigated the relationships between blood pressure, cortical oxygen pressure, and extracellular striatal dopamine in the brain of adult cats during hemorrhagic hypotension and retransfusion. Oxygen pressure in the blood of the cortex was measured by the oxygen dependent quenching of phosphorescence and extracellular dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by in vivo microdialysis. Following a 2 h stabilization period after implantation of the microdialysis probe in the striatum, the mean arterial blood pressure (MAP) was decreased in a stepwise manner from 132 +/- 2 Torr (control) to 90 Torr, 70 Torr and 50 Torr, holding the pressure at each level for 15 min. The whole blood was then retransfused and measurements were continued for 90 min. As the MAP was lowered there was a decrease in arterial pH, from a control value of 7.37 +/- 0.05 to 7.26 +/- 0.06. The PaCO2 decreased during bleeding from 32.3 +/- 4.8 Torr to 19.6 +/- 3.6 Torr and returned to 30.9 +/- 3.9 Torr after retransfusion. The PaO2 was 125.9 +/- 15 Torr during control conditions and did not significantly change during bleeding. Cortical oxygen pressure decreased with decrease in MAP, from 50 +/- 2 Torr (control) to 42 +/- 1 Torr, 31 +/- 2 Torr and 22 +/- 2 Torr, respectively. A statistically significant increase in striatal extracellular dopamine, to 2,580 +/- 714% of control was observed when MAP decreased to below 70 Torr and cortical oxygen pressure decreased to below 31 Torr. When the MAP reached 50 Torr, the concentration of extracellular dopamine increased to 18,359 +/- 2,764% of the control value. A statistically significant decrease in DOPAC and HVA were observed during the last step of bleeding. The data show that decreases in systemic blood pressure result in decrease in oxygen pressure in the microvasculature of the cortex, suggesting vascular dilation is not sufficient to result in a full compensation for the decreased MAP. The decrease in cortical oxygen pressure to below 32 Torr is accompanied by a marked increase in extracellular dopamine in the striatum, indicating that even such mild hypoxia can induce significant disturbance in brain metabolism.
3,4-Dihydroxyphenylacetic Acid↗
The effects of induced apneic episodes on cerebral cortical oxygenation in newborn piglets.
The effect of different inspiratory oxygen levels (FiO2) on cortical oxygenation (pO2) during and after recovery from apnea, was investigated in 18 anesthetized, paralyzed, and mechanically ventilated newborn piglets. Heart rate (HR) and mean arterial blood pressure (MABP) were continuously monitored as the piglets were subjected to repeated episodes of apnea initiated by disconnecting the ventilator and terminated when HR decreased to less than 80 beats/min by reconnecting the ventilator. A closed cranial window was placed over the parietal cortex of the animals and cortical pO2 was measured optically by phosphorescence quenching. Apneic episodes induced in animals ventilated with 15%, 22% and 40% oxygen had mean duration's of apnea (time before HR decreased to less than 80 beats/min) of 80, 128 and 134 s, respectively. By the end of the apnea the MABP decreased to 82%, 64%, and 54% of control, respectively. The cortical pO2 decreased from control values of 24.1, 32.3 and 38.3 Torr at 15%, 22% and 40% oxygen, respectively, to 1.7 to 3.2 Torr at the end of the apneic episode. The duration of apnea necessary for the cortical pO2 to drop below 20.3 Torr was 18, 44 and 81 s at 15%, 22% and 40% oxygen, respectively. There was an inverse correlation between the rate of decline of cortical pO2 and baseline FiO2 levels. With reventilation, the cortical pO2 reached maximal values of 42.8, 51.9 and 57.2 Torr at 15%, 22%, and 40% oxygen, respectively, before returning to the pre-apnea values. The present results show that apnea of less than 30 s duration at an FiO2 of 22% do not result in significant cortical hypoxia in hemodynamically stable piglets. Increasing the FiO2 to above 22% may possibly increase the rate of recovery of tissue oxygenation but it also may facilitate post-hypoxic cortical hyperoxia, a factor that may predispose the immature brain to free radical injury.
Animals↗
The effect of hypoxia and catecholamines on regional expression of heat-shock protein-72 mRNA in neonatal piglet brain.
The present study has shown that hypoxia leads to expression of heat-shock protein in the brain of newborn piglets and this process is almost completely abolished by depletion of catecholamines prior to the hypoxic episode. The piglets were anesthetized and mechanically ventilated. One hour of hypoxia was generated by decreasing the oxygen fraction in the inspired gas (FiO2) from 22% to 6%-10%. FiO2 was then returned to the control value for a period of 2 h. Following the 2 h of reoxygenation, regional expression of the 72-kDa heat-shock protein (hsp72) mRNA was determined using in situ hybridization and autoradiography. The hypoxic insult (cortical pO2 = 3-10 mmHg) induced expression of hsp72 mRNA in regions of both white and gray matter, with strong expression occurring in the cerebral cortex of individual animals. Depleting the brain of catecholamines prior to hypoxia, by treating the animals with alpha-methyl-p-tyrosine (AMT), resulted in a major change in the hsp72 mRNA expression. In the catecholamine depleted group of animals, the intensity of hsp72 mRNA expression was greatly decreased or almost completely abolished relative to the nondepleted hypoxic group. These results suggest that the catecholamines play a significant role in the expression of the hsp72 gene in response to hypoxic insult in neonatal brain.
Animals↗
Effect of hypoxia and reoxygenation on regional activity of nitric oxide synthase in brain of newborn piglets.
The activity of nitric oxide synthase (NOS) was measured in homogenates from cortex, striatum, hippocampus, cerebellum, pons, thalamus and midbrain of the brain of newborn piglets and the effects of hypoxia and posthypoxic period on this activity was evaluated. The control activities were 19.7, 31.5, 26.8, 16.7, 33.6, 19.3 and 39.4 pmol/mg protein per min, respectively. A 1 h period of hypoxia (an FiO2 of 7%) resulted in statistically significant decreases in the activity of NOS in every region of the brain except for the cortex, where the activity was not significantly altered compared to control. By 2 h of reoxygenation following such a hypoxic episode, the NOS activities increased to above control levels in all regions of the brain, but this increase was statistically significant compared to control only in thalamus. Since hypoxia induced the greatest decrease in NOS activity in the cerebellum, the kinetic constants of the enzyme were measured in homogenates from this region of brain. The decreased activity following the hypoxic episode was associated with an approximately four-fold increase in the apparent affinity (KM) for arginine with no significant change in the maximal rate of reaction (Vmax). The decrease in NOS activity subsequent to a hypoxic episode may contribute to the disturbances in cellular metabolism in the immature brain induced by episodes of hypoxia-reoxygenation.
Animals↗
Response of cortical oxygen pressure and striatal extracellular dopamine in the brain of newborn and adult animals to hypoxia.
Explore the source record for details and available documents.
Animals↗
Comparison of postasphyxial resuscitation with 100% and 21% oxygen on cortical oxygen pressure and striatal dopamine metabolism in newborn piglets.
The present study tests the hypothesis that ventilation with 100% O2 during recovery from asphyxia leads to greater disturbance in brain function, as measured by dopamine metabolism, than does ventilation with 21% oxygen. This hypothesis was tested using mechanically ventilated, anesthetized newborn piglets as an animal model. Cortical oxygen pressure was measured by the oxygen-dependent quenching of phosphorescence, striatal blood flow by laser Doppler, and the extra-cellular levels of dopamine and its metabolites by in vivo microdialysis. After establishment of a baseline, both the fraction of inspired oxygen (FiO2) and the ventilator rate were reduced in a stepwise fashion every 20 min over a 1-h period. For the subsequent 2-h recovery, the animals were randomized to breathing 21 or 100% oxygen. It was observed that during asphyxia cortical oxygen pressure decreased from 36 to 7 torr, extracellular dopamine increased 8,300%, and dihydroxyphenylacetic acid and homovanillic acid decreased by 65 and 60%, respectively, compared with controls. During reoxygenation after asphyxia, cortical oxygen pressure was significantly higher in the piglets ventilated with 100% oxygen than in those ventilated with 21% oxygen (19 vs. 11 torr). During the first hour of reoxygenation, extracellular dopamine levels decreased to approximately 200% of control in the 21% oxygen group, whereas these levels were still much higher in the 100% oxygen group (approximately 500% of control). After approximately 2 h of reoxygenation, there was a secondary increase in extracellular dopamine to approximately 750 and approximately 3,000% of baseline for the animals ventilated with 21 and 100%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Relationships of dopamine, cortical oxygen pressure, and hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic recovery.
The present study describes the relationships of extracellular striatal dopamine, cortical oxygen pressure, and striatal hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic reoxygenation. Hypoxia was induced by reducing the fraction of inspired oxygen (FiO2) from 22% (control) to 7% for 1 h. The FiO2 was then returned to the control value and measurements were continued for 2 h. Cerebral oxygen pressure was measured by the oxygen dependent quenching of phosphorescence and extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and hydroxy radicals in the striatum were determined by in vivo microdialysis. Hypoxia decreased the cortical oxygen pressure from 47 +/- 2 to 9 +/- 1.3 torr (p < 0.001); the levels of extracellular dopamine in the striatum increased to 16,000 +/- 3,270% of control (p < 0.01), whereas the levels of DOPAC and HVA decreased to 25.3 +/- 6% (p < 0.001) and 36 +/- 5% (p < 0.01) of control, respectively. Compared with control, the hydroxyl radical levels at each time point were not significantly increased during hypoxia, although the sum of the measured values was significantly increased (p < 0.05). During the first 5 min after FiO2 was returned to 22%, the cortical oxygen pressure increased to control values and stayed at this level for the remainder of the measurement period. The extracellular level of dopamine declined to values not statistically different from control during 40 min of reoxygenation. During the first 10 min of reoxygenation, DOPAC and HVA further decreased and then began to slowly increase. By 70 min of reoxygenation, the values were not significantly different from control.(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dihydroxyphenylacetic Acid↗
Comparison of the efficacy of blood and polyethylene glycol-hemoglobin in recovery of newborn piglets from hemorrhagic hypotension: effect on blood pressure, cortical oxygen, and extracellular dopamine in the brain.
BACKGROUND: Successful blood substitutes, when infused in place of an equal volume of whole blood, provide similar delivery of oxygen to the tissues without introducing abnormalities in cellular metabolism. STUDY DESIGN AND METHODS: Equal volumes of whole blood (control), polyethylene glycol-hemoglobin solution at 6 g per dL, dextran solution, and physiologic saline were compared for their ability to reverse the effects of hemorrhagic hypotension on oxygenation and dopamine metabolism in the brain of newborn piglets. The decrease in mean arterial blood pressure was used as a measure of the hemorrhagic insult. Cerebral oxygen pressure was determined optically by the oxygen-dependent quenching of phosphorescence, and the extracellular level of dopamine in the corpus striatum was determined by in vivo microdialysis. RESULTS: Following a 2-hour stabilization after implantation of the microdialysis probe in the corpus striatum, the mean arterial blood pressure was decreased from 88 +/- 7 torr (control) to 42 +/- 5 torr by the removal of blood in a stepwise manner, over a period of 60 minutes. Decrease in mean arterial blood pressure caused a progressive stepwise decrease in cortical oxygen pressure from 48 +/- 5 torr to 16 +/- 4 torr at the end of bleeding. As a consequence of the decrease in oxygen pressure, extracellular dopamine increased progressively to about 2300 percent of the control value. When a volume of blood equal to that removed was returned and bicarbonate was injected to help correct arterial pH, blood pressure, cortical oxygen pressure, and extracellular dopamine all returned within the 20- to 30-minute recovery period to values not significantly different from control values. An equal volume of polyethylene glycol-hemoglobin solution, even with significantly lower hemoglobin content than whole blood, gave results comparable to those with whole blood. CONCLUSION: Polyethylene glycol-hemoglobin solution, like whole blood but in contrast to physiologic saline or dextran solution, was capable of returning the mean arterial blood pressure, cortical oxygen pressures, and extracellular dopamine nearly to control levels after acute blood loss in newborn piglets.
Animals↗
Effect of hemorrhagic hypotension on extracellular level of dopamine, cortical oxygen pressure and blood flow in brain of newborn piglets.
The present study describes the relationships between extracellular striatal dopamine, cortical oxygen pressure and blood flow in brain of newborn piglets during hemorrhagic hypotension. Cerebral oxygen pressure was measured optically by the oxygen dependent quenching of phosphorescence; extracellular dopamine by in vivo microdialysis; striatal blood flow was monitored by a laser Doppler. Following a 2 h stabilization period after implanting the microdialysis and laser Doppler probes in the striatum, the mean arterial blood pressure (MABP) was decreased in stepwise manner from 87 +/- 4 Torr (control) to 35 +/- 5 Torr, during 63 min. The whole blood was then reinfused and measurements were continued for 45 min. Statistically significant decrease in blood flow, 10%, was observed when arterial blood pressure decreased to about 53 Torr. With further decrease blood pressure to 35 Torr, blood flow decreased to about 35% of control (P < 0.01). Cortical oxygen pressure decreased almost proportional to decrease in blood pressure. The progressive decrease in MABP from 87 +/- 4 Torr to 65 +/- 6, 52 +/- 7, and 35 +/- 5 Torr resulted in cortical oxygen pressure decreasing from 45 +/- 4 Torr to 33 +/- 3 Torr (P < 0.05), 24 +/- 4 Torr (P < 0.01) and 13 +/- 3 Torr (P < 0.01). The levels of extracellular dopamine in the striatum increased with decreasing cortical oxygen pressure. As cortical oxygen decreased, the extracellular dopamine increased to 230%, 420% and 3200% of control, respectively. Our results show that in mild hypotension total blood flow is well maintained but oxygen pressure in the microvasculature decreases, possibly due to heterogeneity in the regulatory mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dihydroxyphenylacetic Acid↗
Effect of hypoxia and reoxygenation on the activity of transglutaminase in brain of newborn piglets.
The transglutaminase activity in five regions of the brain of newborn piglets was measured and the effects of hypoxia and posthypoxic period on this activity evaluated. Enzyme activity was measured in homogenates from cortex, hippocampus, striatum, thalamus and midbrain. The control activities were 7.2, 6.2, 6.0, 5.7 and 4.6 pmol/mg protein/min, respectively. The activities at the end of an 18 min period of hypoxia induced by an FiO2 of 9% were not significantly different from control activities. By 3 h after the hypoxic episode, however, the transglutaminase activities were significantly above control levels in all five regions of the brain. Measurements of the kinetic constants of tranglutaminase indicated that increases in enzyme activity were associated with an increase in Vmax with no significant change in the apparent affinity of the enzyme for the substrate, putrescine. The increased activity of transglutaminase during the posthypoxic period, with no changes immediately after hypoxia, suggest that the increases could be due to increased enzyme synthesis rather than activation of existing enzyme. The rise in transglutaminase activity subsequent to a hypoxic episode may contribute significantly to the long-term disturbances in cellular metabolism in the immature brain induced by hypoxic episodes.
Animals↗
Metabolic responses of the dopaminergic system during hypoxia in newborn brain.
The purpose of this review is to describe the relationship between the dopamine and amino acid neurotransmitter systems and cortical oxygen pressure during different levels of cerebral hypoxia using newborn piglets as an animal model, adding new data from our laboratory. The extracellular dopamine increases as the oxygen pressure in the cortex decreases. The relationship between oxygen pressure and dopamine levels is the same whether the hypoxia is induced by reduced FiO2 (high-flow hypoxia) or by hypocapnia-induced cerebral vasoconstriction (low-flow hypoxia). Thus it appears that, particularly in mild hypoxia, the extracellular level of dopamine depends primarily on the oxygen concentration in the tissue with minimal influence of parameters such as blood flow and pH. There is no "oxygen reserve" in the brain of newborn piglets and the extracellular levels of dopamine in the striatum increase almost linearly with decrease in oxygen pressure, with even small decreases in oxygen pressure resulting in increased dopamine levels. In contrast, the changes in extracellular concentrations of the excitatory amino acids glutamate and aspartate are variable and transient. In a majority of 2- to 5-day-old piglets even very low oxygen pressures in the brain did not result in significant alterations in the extracellular levels of glutamate and aspartate. These changes in the dopaminergic system may contribute directly and indirectly to the neuronal damage that occurs during hypoxic/ischemic insult and reoxygenation in newborn brain, particularly in the striatum. A variety of mechanisms are discussed by which dopamine, in particular extracellular dopamine, can increase cellular toxicity.
Animals↗
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.
Animals↗