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In vivo dopaminergic and behavioral responses to acute cocaine are altered in adenosine A(2A) receptor knockout mice.
- Source :
-
Synapse (New York, N.Y.) [Synapse] 2012 May; Vol. 66 (5), pp. 383-90. Date of Electronic Publication: 2012 Feb 15. - Publication Year :
- 2012
-
Abstract
- Adenosine, acting on adenosine A(2A) receptors (A2ARs), regulates addictive processes induced by drugs of abuse. This study investigates the role of A(2A) adenosine receptors in neurochemical and behavioral responses to an acute cocaine challenge. Changes in the extracellular levels of dopamine (DA) in the nucleus accumbens (NAc) of mice lacking A(2A) adenosine receptors and wild type (WT) littermates after an acute cocaine (20 mg/kg) administration were evaluated by in vivo microdialysis studies. Locomotor effects induced by cocaine were measured during the microdialysis procedure. Cocaine-evoked increases in extracellular DA were not sustained in mice lacking A(2A) Rs in comparison with wild-type mice (P < 0.05). Cocaine administration significantly increased ambulatory activity in both genotypes. However, overall locomotor activity was further increased, whereas rest and small local movement measures were significantly attenuated in the A(2A) R knockout mice compared with WT littermates (P < 0.05). Our findings support an important role for adenosine A(2A) R in modulating the acute effects of cocaine, as demonstrated by the decrease in cocaine-evoked dopaminergic transmission in the NAc. Furthermore, the results support an important antagonistic role of A(2A) R in vivo in regulating psychostimulant-induced hyperlocomotion.<br /> (Copyright © 2011 Wiley Periodicals, Inc.)
- Subjects :
- Animals
Behavior, Animal drug effects
Male
Mice
Mice, Knockout
Microdialysis
Receptor, Adenosine A2A physiology
Cocaine pharmacology
Dopamine metabolism
Dopamine Uptake Inhibitors pharmacology
Locomotion drug effects
Motor Activity drug effects
Nucleus Accumbens drug effects
Receptor, Adenosine A2A genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-2396
- Volume :
- 66
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Synapse (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 22213208
- Full Text :
- https://doi.org/10.1002/syn.21527