Role of serotonin and/or norepinephrine in the MDMA-induced increase in extracellular glucose and glycogenolysis in the rat brain

Pachmerhiwala, Rashida; Bhide, Nirmal; Straiko, Michael D.; Gudelsky, Gary A.

doi:10.1016/j.ejphar.2010.07.004

Cited by 12 publications

(8 citation statements)

References 33 publications

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“…Furthermore, as shown in Figures 4G and 4H, the decrease in cortical glycogen levels during exercise was negatively correlated with increased cortical MHPG and 5-HIAA levels. Since brain glycogenolysis is promoted by activation of noradrenergic and/or serotonergic mechanisms (Benington & Heller, 1995;Pachmerhiwala et al, 2010), our present results suggest that the reduction of cortex glycogen during exercise is not only due to hypoglycemia but also to increased NA and 5-HT metabolism. In addition, since neuronal activation would promote NA and 5-HT metabolisms, our results suggest that cortical neuronal activity increases with exercise.…”

Section: Discussionmentioning

confidence: 57%

Brain glycogen decreases during prolonged exercise

Matsui¹,

Soya²,

Okamoto³

et al. 2011

The Journal of Physiology

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Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here,we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose,we exercised male Wistar rats on a treadmill for different durations (30-120 min) at moderate intensity (20 m min⁻¹) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37-60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise.

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Section: Discussionmentioning

confidence: 57%

Brain glycogen decreases during prolonged exercise

Matsui¹,

Soya²,

Okamoto³

et al. 2011

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…4 and , the decrease in cortical glycogen levels during exercise was negatively correlated with increased cortical MHPG and 5‐HIAA levels. Since brain glycogenolysis is promoted by activation of noradrenergic and/or serotonergic mechanisms (Benington & Heller, 1995; Pachmerhiwala et al 2010), our present results suggest that the reduction of cortex glycogen during exercise is not only due to hypoglycaemia but also to increased NA and 5‐HT metabolism. In addition, since neuronal activation would promote NA and 5‐HT metabolism, our results suggest that cortical neuronal activity increases with exercise.…”

Section: Discussionmentioning

confidence: 63%

Brain glycogen decreases during prolonged exercise

Matsui¹,

Soya²,

Okamoto³

et al. 2011

The Journal of Physiology

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Non-technical summary Energy sources for the brain include not only blood glucose, but also astrocytic glycogen, especially when the blood-born glucose supply is short (e.g. hypoglycaemia). Although untested, it is hypothesized that during prolonged exercise that induces hypoglycaemia, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and provide evidence that brain glycogen decreases during prolonged exercise with hypoglycaemia. Furthermore, in the cortex, we show that the decrease in brain glycogen levels during prolonged exercise is associated with activation of monoamine metabolism, which could be a factor inducing central fatigue. Since the discovery of muscle glycogen depletion as a candidate of peripheral fatigue during prolonged exercise, this is the first study to our knowledge to show that brain glycogen can decrease with prolonged exercise. These findings may provide a clue towards understanding the mechanisms related to central fatigue.Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30-120 min) at moderate intensity (20 m min −1 ) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37-60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise.

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“…However, reverse dialysis of MDMA also evoked an increase in glutamate efflux in the absence of behavioral activation or hyperthermia. Moreover, fluoxetine diminished the glutamate response to MDMA despite the fact that fluoxetine does not diminish MDMA-induced hyperthermia (Malberg et al, 1996; Pachmerhiwala et al, 2010). Thus, hyperthermia per se appears to be neither necessary nor sufficient to increase extracellular glutamate in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

MDMA produces a delayed and sustained increase in the extracellular concentration of glutamate in the rat hippocampus

Anneken

Gudelsky

2012

Neuropharmacology

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The neurochemical effects of MDMA (3,4-methylenedioxymethamphetamine) on monoaminergic and cholinergic systems in the rat brain have been well documented. However, little is known regarding the effects of MDMA on glutamatergic systems in the brain. In the present study the effects of multiple injections of MDMA on extracellular concentrations of glutamate in the striatum, prefrontal cortex, and dorsal hippocampus were examined. Two or four, but not one, injections of MDMA (10 mg/kg, i.p. at 2 h intervals) resulted in a 2–3 fold increase in the extracellular concentration of glutamate in the hippocampus; no increase was evident in the striatum or prefrontal cortex. Reverse dialysis of MDMA (100 µM) into the hippocampus also elicited an increase in extracellular glutamate. Treatment with the 5-HT reuptake inhibitor fluoxetine prevented the increase in extracellular glutamate in the hippocampus following the systemic administration of MDMA, as did treatment with the serotonin 5-HT2A/C receptor antagonist ketanserin. Moreover, reverse dialysis of the sodium channel blocker tetrodotoxin did not prevent the increase in extracellular glutamate in the hippocampus. These data support the view that stimulation of 5-HT2A/2C receptors on non-neuronal cells by 5-HT released by MDMA promotes glutamate efflux in the hippocampus.

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Role of serotonin and/or norepinephrine in the MDMA-induced increase in extracellular glucose and glycogenolysis in the rat brain

Cited by 12 publications

References 33 publications

Brain glycogen decreases during prolonged exercise

Brain glycogen decreases during prolonged exercise

Brain glycogen decreases during prolonged exercise

MDMA produces a delayed and sustained increase in the extracellular concentration of glutamate in the rat hippocampus

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