Acute tryptophan depletion potentiates 3,4-methylenedioxymethamphetamine-induced cerebrovascular hyperperfusion in adult male Wistar rats

Autor: Harry W.M. Steinbusch, Linda Ferrington, Eva L. van Donkelaar, Paul A.T. Kelly, Arjan Blokland, Neil Dawson, Jos Prickaerts
Přispěvatelé: Neuropsychology & Psychopharmacology, Psychiatrie & Neuropsychologie, RS: FPN NPPP II
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Male
Ecstasy
flow-metabolism coupling
Serotonin Agents
Serotonin Plasma Membrane Transport Proteins
Tryptophan
Brain
MDMA
Paroxetine
Pathophysiology
5-HT RELEASE
serotonin
Vasodilation
Cerebrovascular Circulation
cerebrovascular dysfunction
RHESUS-MONKEYS
medicine.drug
plasma tryptophan
medicine.medical_specialty
IMPAIRS OBJECT MEMORY
N-Methyl-3
4-methylenedioxyamphetamine
NEUTRAL AMINO-ACIDS
GELATIN-BASED MIXTURE
Hyperemia
Serotonergic
Binding
Competitive
COGNITIVE PERFORMANCE
Cellular and Molecular Neuroscience
GLUCOSE-UTILIZATION
Internal medicine
medicine
SEROTONIN UPTAKE SITES
Animals
Rats
Wistar
NITRIC-OXIDE SYNTHASE
5-HT receptor
Depressive Disorder
business.industry
Neurotoxicity
Cerebral Arteries
medicine.disease
ecstacy
Rats
Cerebrovascular Disorders
Disease Models
Animal
Endocrinology
CEREBRAL-BLOOD-FLOW
business
Zdroj: Journal of Neuroscience Research, 88(7), 1557-1568. Wiley-Liss Inc.
ISSN: 0360-4012
DOI: 10.1002/jnr.22308
Popis: The serotonergic (5-hydroxytryptannine; 5-HT) dysfunction found in depression may affect not only brain function (mood) but also cerebrovascular control. Similar, but possibly occult, disturbances may also be induced by 3,4-methylenedioxymethamphetamine-induced neurotoxicty (MDMA, or "ecstasy"). Acute tryptophan depletion (AID) is widely used to identify vulnerability to depression, and we hypothesized that repeated MDMA administration would increase the sensitivity of rats to this acute serotonergic challenge. In this study, male Wistar rats were injected with MDMA (20 mg . kg(-1), twice daily for 4 days) and challenged 3 weeks later with ATD, induced by intragastric administration of a nutritional mixture with tryptophan (TRP) removed. Cerebral metabolism (CMRG) and blood flow (CBF) were measured in parallel groups of animals following AID by using quantitative [C-14]2-deoxyglucose and [C-14]iodoantipyrine autoradiographic techniques, respectively. A significant reduction in paroxetine binding to 5-HT transporter sites in MDMA-treated rats indicated 5HT terminal depletion, whereas the plasma TRP/sum large neutral amino acids ratio was reduced by 40% following AID. Under all experimental conditions, the normal close correlation between CBF and metabolic demand was maintained. However, a global analysis of all brain regions revealed a significant decrease in the overall ratio of CBF to CMRG after AID in control animals, whereas a higher ratio was observed after AID in the MDMA-treated group. This increase in blood flow relative to cerebral metabolism suggests an ATD-induced loss of cerebrovascular tone in MDMA-treated animals that could have pathophysiological consequences and might conceivably contribute to the behavioral dysfunction of depression. (C) 2009 Wiley-Liss, Inc.
Databáze: OpenAIRE
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