Cannabis induced increase in striatal glutamate associated with loss of functional corticostriatal connectivity

Autor: Natasha L. Mason, Eef L. Theunissen, Johannes G. Ramaekers, Peter Stiers, Stefan W. Toennes, Nadia R P W Hutten, Desmond H. Y. Tse
Přispěvatelé: Section Psychopharmacology, RS: FPN NPPP II, Section Neuropsychology, RS: FPN NPPP I
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Cannabinoid receptor
Magnetic Resonance Spectroscopy
Visual Analog Scale
Dopamine
HUMAN-BRAIN
Pharmacology
Functional connectivity
0302 clinical medicine
Limbic system
Delta-9-tetrahydrocannabinol
Neural Pathways
DOPAMINE RELEASE
Pharmacology (medical)
Dronabinol
Correlation of Data
IN-VIVO
Cerebral Cortex
Chemistry
Dopaminergic
Glutamate receptor
Magnetic Resonance Imaging
CB1
Healthy Volunteers
Psychiatry and Mental health
medicine.anatomical_structure
Neurology
Female
Glutamate
USERS
medicine.drug
Adult
THC
Rest
NUCLEUS-ACCUMBENS
Glutamic Acid
Nucleus accumbens
03 medical and health sciences
Double-Blind Method
SUPERIOR FRONTAL GYRUS
mental disorders
medicine
Humans
Biological Psychiatry
Effects of cannabis
Cannabis
Proton magnetic resonance spectroscopy
Dose-Response Relationship
Drug
organic chemicals
DELTA(9)-TETRAHYDROCANNABINOL
Corpus Striatum
030227 psychiatry
Oxygen
Cross-Sectional Studies
MARIJUANA
Neurology (clinical)
DELTA-9-TETRAHYDROCANNABINOL
030217 neurology & neurosurgery
Psychomotor Performance
Zdroj: European Neuropsychopharmacology, 29(2), 247-256. Elsevier
ISSN: 0924-977X
DOI: 10.1016/j.euroneuro.2018.12.003
Popis: Cannabis is the most commonly used illicit drug and is known to alter state of consciousness and impair neurocognitive function. However, the mechanisms underlying these effects have yet to be fully elucidated. Rodent studies suggest that Delta 9-tetrahydrocannabinol (THC) activates dopaminergic neurons in the limbic system, subsequently enhancing dopamine, which is implicated in the rewarding effects of cannabis. Additional evidence suggests that THC may act indirectly on dopamine firing by modulating GABA and glutamate release. This double-blind, placebo-controlled study assessed the acute influence of two doses of THC on brain kinetics of glutamate, GABA, and dopamine, in relation to behavioral outcomes, by using magnetic resonance spectroscopy and functional magnetic resonance imaging. Twenty occasional cannabis users received acute doses of cannabis (300 mu g/kg THC) and placebo, in one of two dose regimes (full dose and divided dose), during two separate testing days. Administration of THC increased striatal glutamate concentrations, and dopamine as indicated by a reduction in functional connectivity (FC) between the nucleus accumbens (NAc) and cortical areas. Alterations in glutamate and FC were dose dependent and evident in the full dose group where THC serum concentrations exceeded 2 ng/ml at T-max. Average glutamate changes correlated strongly with FC alterations. Additionally, THC induced changes in FC correlated with feelings of subjective high and decreased performance on an attention task. Taken together, this suggests that THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity, which is associated with an increase in striatal glutamate. (c) 2018 Elsevier B.V. and ECNP. All rights reserved.
Databáze: OpenAIRE
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