Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) administration in awake rats

Gramsbergen, Jan Bert; Cumming, Paul

doi:10.1016/j.neuint.2007.03.004

Cited by 12 publications

(15 citation statements)

References 46 publications

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“…For example, MDMA increases extracellular glucose in multiple brain regions (Pachmerhiwala et al, 2010), especially within striatum (Darvesh et al, 2002; Gramsbergen and Cumming, 2007). MDMA also reduces the brain concentration of glycogen, one of the main energy reserves in brain (Darvesh and Gudelsky, 2004; Darvesh et al, 2002).…”

Section: Brain Energy Regulation and Psychostimulant Exposurementioning

confidence: 99%

Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

Downey

Loftis

2014

European Journal of Pharmacology

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Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes – increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment.

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Section: Brain Energy Regulation and Psychostimulant Exposurementioning

confidence: 99%

Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

Downey

Loftis

2014

European Journal of Pharmacology

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“…The systemic administration of MDMA results in a prolonged increase in the extracellular concentration of glucose in the striatum, hippocampus and prefrontal cortex (Darvesh et al, 2002;Pachmerhiwala et al, 2007;Gramsbergen and Cumming, 2007), as well as the extracellular concentration of lactate in the striatum (Gramsbergen and Cumming, 2007). The MDMA-induced increase in the extracellular concentration of energy substrates is prevented in rats in which 5-HT synthesis has been inhibited or in rats treated with a 5-HT reuptake inhibitor (e.g., fluoxetine) (Gramsbergen and Cumming, 2007;Pachmerhiwala et al, 2007). Pachmerhiwala et al (2007) also reported that adrenergic receptor antagonists prevent the increased glucose response to MDMA.…”

Section: Energy Substratesmentioning

confidence: 99%

“…Although Darvesh et al (2002) originally suggested that the increase in brain extracellular glucose following MDMA may be a result of MDMA-induced glycogenolysis in brain, Gramsbergen and Cumming (2007) have speculated that increased brain glucose produced by MDMA is a result of increased peripheral blood glucose and increased glucose transport into brain, since these investigators have reported that MDMA produces a transient increase in peripheral blood glucose. However, other investigators have failed to confirm an effect of MDMA to increase blood glucose.…”

Section: Energy Substratesmentioning

confidence: 99%

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

Gudelsky

Yamamoto

2008

Pharmacology Biochemistry and Behavior

120

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Abstract3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative and a popular drug of abuse that exhibits mild hallucinogenic and rewarding properties and engenders feelings of connectedness and openness. The unique psychopharmacological profile of this drug of abuse most likely is derived from the property of MDMA to promote the release of dopamine and serotonin (5-HT) in multiple brain regions. The present review highlights primarily data from studies employing in vivo microdialysis that detail the actions of MDMA on the release of these neurotransmitters. Data from in vivo microdialysis experiments indicate that MDMA, like most amphetamine derivatives, increases the release of dopamine in the striatum, n. accumbens and prefrontal cortex. However, the release of dopamine evoked by MDMA in each of these brain regions appears to be modulated by concomitantly released 5-HT and the subsequent activation of 5-HT2A/C or 5-HT2B/C receptors. In addition to its stimulatory effect on the release of monoamines, MDMA also enhances the release of acetylcholine in the striatum, hippocampus and prefrontal cortex, and this cholinergic response appears to be secondary to the activation of histaminergic, dopaminergic and/or serotonergic receptors. Beyond the acute stimulatory effect of MDMA on neurotransmitter release, MDMA also increases the extracellular concentration of energy substrates, e.g., glucose and lactate in the brain. In contrast to the acute stimulatory actions of MDMA on the release of monoamines and acetylcholine, the repeated administration of high doses of MDMA is thought to result in a selective neurotoxicity to 5-HT axon terminals in the rat. Additional studies are reviewed that focus on the alterations in neurotransmitter responses to pharmacological and physiological stimuli that accompany MDMA-induced 5-HT neurotoxicity.

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“…Under in vitro conditions, MDMA increases the activity of glycogen phosphorylase, an enzyme responsible for the breakdown of glycogen, in astro-glial rich primary cultures (Poblete and Azmitia, 1995). Furthermore, extracellular concentrations of glucose and lactate in the striatum are increased following MDMA administration (Darvesh et al, 2002; Gramsbergen and Cumming, 2007). In previous reports it has been suggested that activation of 5-HT2 receptors and/or hyperthermia contribute to the mechanism of substituted amphetamine-induced glycogenolysis and increased extracellular glucose in the brain (Huether et al, 1997; Darvesh et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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

Pachmerhiwala

Bhide

Straiko

et al. 2010

European Journal of Pharmacology

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The acute administration of MDMA has been shown to promote glycogenolysis and increase the extracellular concentration of glucose in the striatum. In the present study the role of serotonergic and/or noradrenergic mechanisms in the MDMA-induced increase in extracellular glucose and glycogenolysis was assessed. The relationship of these responses to the hyperthermia produced by MDMA also was examined. The administration of MDMA (10 mg/kg, i.p.) resulted in a significant and sustained increase of 65-100% in the extracellular concentration of glucose in the striatum, as well as in the prefrontal cortex and hippocampus, and a 35% decrease in brain glycogen content. Peripheral blood glucose was modestly increased by 32% after MDMA treatment. Treatment of rats with fluoxetine (10 mg/kg, i.p.) significantly attenuated the MDMAinduced increase in extracellular glucose in the striatum but had no effect on MDMA-induced glycogenolysis or hyperthermia. Treatment with prazosin (1 mg/kg, i.p.) did not alter the glucose or glycogen responses to MDMA but completely suppressed MDMA-induced hyperthermia. Finally, propranolol (3 mg/kg, i.p.) significantly attenuated the MDMA-induced increase in extracellular glucose and glycogenolysis but did not alter MDMA-induced hyperthermia. The present results suggest that MDMA increases extracellular glucose in multiple brain regions, and that this response involves both serotonergic and noradrenergic mechanisms. Furthermore, β-adrenergic and α-adrenergic receptors appear to contribute to MDMA-induced glycogenolysis and hyperthermia, respectively. Finally, hyperthermia, glycogenolysis and elevated extracellular glucose appear to be independent, unrelated responses to acute MDMA administration.

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Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) administration in awake rats

Cited by 12 publications

References 46 publications

Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

Actions of 3,4-methylenedioxymethamphetamine (MDMA) on cerebral dopaminergic, serotonergic and cholinergic neurons

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

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