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

Jan Bert Gramsbergen, Paul Cumming

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

 
Udgivelsesdato: 2007-Jul
OriginalsprogEngelsk
TidsskriftNeurochemistry International
Vol/bind51
Udgave nummer1
Sider (fra-til)8-15
Antal sider7
ISSN0197-0186
DOI
StatusUdgivet - 1. jul. 2007

Fingeraftryk

N-Methyl-3,4-methylenedioxyamphetamine
Lactic Acid
Fenclonine
Flow Injection Analysis
Microdialysis
Biosensing Techniques
Energy Metabolism
Pharmaceutical Preparations

Citer dette

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title = "Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, {"}Ecstasy{"}) administration in awake rats.",
abstract = " The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, {"}Ecstasy{"}) is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose metabolism in freely moving rats using rapid sampling microdialysis (every minute) coupled to flow-injection analysis (FIA) with biosensors for glucose and lactate. Blood samples for analysis of glucose and lactate were taken at 30-45 min intervals before and after drug dosing and body temperature was monitored by telemetry. A single dose of MDMA (2-10-20 mg/kg i.v.) evoked a transient increase of interstitial glucose concentrations in striatum (139-223{\%}) with rapid onset and of less than 2h duration, a concomitant but more prolonged lactate increase (>187{\%}) at the highest MDMA dose and no significant depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135{\%}) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1.1 degrees C) following systemic MDMA treatment were entirely blocked in p-chlorophenylalanine pre-treated rats, indicating that these effects are mediated by endogenous serotonin.",
keywords = "Animals, Body Temperature, Corpus Striatum, Dose-Response Relationship, Drug, Energy Metabolism, Extracellular Fluid, Fenclonine, Fever, Glucose, Lactic Acid, Male, Microdialysis, N-Methyl-3,4-methylenedioxyamphetamine, Rats, Rats, Sprague-Dawley, Serotonin, Serotonin Agents, Serotonin Antagonists, Time Factors, Wakefulness",
author = "Gramsbergen, {Jan Bert} and Paul Cumming",
year = "2007",
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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. / Gramsbergen, Jan Bert; Cumming, Paul.

I: Neurochemistry International, Bind 51, Nr. 1, 01.07.2007, s. 8-15.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") administration in awake rats.

AU - Gramsbergen, Jan Bert

AU - Cumming, Paul

PY - 2007/7/1

Y1 - 2007/7/1

N2 -  The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose metabolism in freely moving rats using rapid sampling microdialysis (every minute) coupled to flow-injection analysis (FIA) with biosensors for glucose and lactate. Blood samples for analysis of glucose and lactate were taken at 30-45 min intervals before and after drug dosing and body temperature was monitored by telemetry. A single dose of MDMA (2-10-20 mg/kg i.v.) evoked a transient increase of interstitial glucose concentrations in striatum (139-223%) with rapid onset and of less than 2h duration, a concomitant but more prolonged lactate increase (>187%) at the highest MDMA dose and no significant depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135%) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1.1 degrees C) following systemic MDMA treatment were entirely blocked in p-chlorophenylalanine pre-treated rats, indicating that these effects are mediated by endogenous serotonin.

AB -  The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose metabolism in freely moving rats using rapid sampling microdialysis (every minute) coupled to flow-injection analysis (FIA) with biosensors for glucose and lactate. Blood samples for analysis of glucose and lactate were taken at 30-45 min intervals before and after drug dosing and body temperature was monitored by telemetry. A single dose of MDMA (2-10-20 mg/kg i.v.) evoked a transient increase of interstitial glucose concentrations in striatum (139-223%) with rapid onset and of less than 2h duration, a concomitant but more prolonged lactate increase (>187%) at the highest MDMA dose and no significant depletions of striatal serotonin. Blood glucose and lactate levels were also transiently elevated (163 and 135%) at the highest MDMA doses. The blood glucose rises were significantly related to brain glucose and brain lactate changes. The metabolic perturbations in striatum and the hyperthermic response (+1.1 degrees C) following systemic MDMA treatment were entirely blocked in p-chlorophenylalanine pre-treated rats, indicating that these effects are mediated by endogenous serotonin.

KW - Animals

KW - Body Temperature

KW - Corpus Striatum

KW - Dose-Response Relationship, Drug

KW - Energy Metabolism

KW - Extracellular Fluid

KW - Fenclonine

KW - Fever

KW - Glucose

KW - Lactic Acid

KW - Male

KW - Microdialysis

KW - N-Methyl-3,4-methylenedioxyamphetamine

KW - Rats

KW - Rats, Sprague-Dawley

KW - Serotonin

KW - Serotonin Agents

KW - Serotonin Antagonists

KW - Time Factors

KW - Wakefulness

U2 - 10.1016/j.neuint.2007.03.004

DO - 10.1016/j.neuint.2007.03.004

M3 - Journal article

VL - 51

SP - 8

EP - 15

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

IS - 1

ER -