Varying the rate of intravenous cocaine infusion influences the temporal dynamics of both drug and dopamine concentrations in the striatum.
Administration, Intravaginal
Animals
Brain
/ drug effects
Cocaine
/ administration & dosage
Cocaine-Related Disorders
/ physiopathology
Corpus Striatum
/ drug effects
Dopamine
/ pharmacology
Dopamine Uptake Inhibitors
/ pharmacology
Locomotion
/ drug effects
Male
Motor Activity
/ drug effects
Neostriatum
/ drug effects
Rats, Wistar
cocaine addiction
in vivo microdialysis
locomotor activity
male Wistar rats
pharmacokinetics
Journal
The European journal of neuroscience
ISSN: 1460-9568
Titre abrégé: Eur J Neurosci
Pays: France
ID NLM: 8918110
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
08
12
2017
revised:
26
03
2018
accepted:
27
03
2018
pubmed:
15
5
2018
medline:
1
7
2020
entrez:
15
5
2018
Statut:
ppublish
Résumé
The faster drugs of abuse reach the brain, the greater is the risk of addiction. Even small differences in the rate of drug delivery can influence outcome. Infusing cocaine intravenously over 5 vs. 90-100 s promotes sensitization to the psychomotor and incentive motivational effects of the drug and preferentially recruits mesocorticolimbic regions. It remains unclear whether these effects are due to differences in how fast and/or how much drug reaches the brain. Here, we predicted that varying the rate of intravenous cocaine infusion between 5 and 90 s produces different rates of rise of brain drug concentrations, while producing similar peak concentrations. Freely moving male Wistar rats received acute intravenous cocaine infusions (2.0 mg/kg/infusion) over 5, 45 and 90 s. We measured cocaine concentrations in the dorsal striatum using rapid-sampling microdialysis (1 sample/min) and high-performance liquid chromatography-tandem mass spectrometry. We also measured extracellular concentrations of dopamine and other neurochemicals. Regardless of infusion rate, acute cocaine did not change concentrations of non-dopaminergic neurochemicals. Infusion rate did not significantly influence peak concentrations of cocaine or dopamine, but concentrations increased faster following 5-s infusions. We also assessed psychomotor activity as a function of cocaine infusion rate. Infusion rate did not significantly influence total locomotion, but locomotion increased earlier following 5-s infusions. Thus, small differences in the rate of cocaine delivery influence both the rate of rise of drug and dopamine concentrations, and psychomotor activity. A faster rate of rise of drug and dopamine concentrations might be an important issue in making rapidly delivered cocaine more addictive.
Identifiants
pubmed: 29757478
doi: 10.1111/ejn.13941
pmc: PMC6296906
mid: NIHMS987560
doi:
Substances chimiques
Dopamine Uptake Inhibitors
0
Cocaine
I5Y540LHVR
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2054-2064Subventions
Organisme : Sciences and Engineering Research Council (NSERC) of Canada
ID : RGPIN-2016-06653
Pays : International
Organisme : Fonds de Recherche du Québec - Santé
ID : 29651
Pays : International
Organisme : NIBIB NIH HHS
ID : R01 EB003320
Pays : United States
Organisme : NIDA NIH HHS
ID : T32 DA007268
Pays : United States
Organisme : Canada Foundation for Innovation
ID : 24326
Pays : International
Organisme : Fonds de Recherche du Québec - Santé
ID : 28988
Pays : International
Organisme : Fonds de Recherche du Québec - Nature et Technologies
Pays : International
Organisme : NIBIB NIH HHS
ID : R37 EB003320
Pays : United States
Organisme : Natural Sciences and Engineering Research Council of Canada
Pays : International
Organisme : Michael J. Fox Foundation for Parkinson's Research
ID : BioFind and Dyskinesia Challenge - awarded to OSM
Pays : International
Informations de copyright
© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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