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Loss of striatal cannabinoid CB1 receptor function in attention-deficit / hyperactivity disorder mice with point-mutation of the dopamine transporter.
- Source :
-
The European journal of neuroscience [Eur J Neurosci] 2011 Nov; Vol. 34 (9), pp. 1369-77. - Publication Year :
- 2011
-
Abstract
- Abnormal dopamine (DA) transmission in the striatum plays a pivotal role in attention-deficit/hyperactivity disorder (ADHD). As striatal DA signalling modulates the endocannabinoid system (ECS), the present study was aimed at investigating cannabinoid CB1 receptor (CB1R) function in a model of ADHD obtained by triple point-mutation in the dopamine transporter (DAT) gene in mice, making them insensitive to cocaine [DAT cocaine-insensitive (DAT-CI) mice]. DAT-CI mice had a marked hyperactive phenotype, and neurophysiological recordings revealed that the sensitivity of CB1Rs controlling GABA-mediated synaptic currents [CB1Rs((GABA)) ] in the striatum was completely lost. In contrast, CB1Rs modulating glutamate transmission [CB1Rs((Glu)) ], and GABA(B) receptors were not affected in this model of ADHD. In DAT-CI mice, the blockade of CB1R((GABA)) function was complete even after cocaine or environmental manipulations activating the endogenous DA-dependent reward system, which are known to sensitize these receptors in control animals. Conversely, the hedonic property of sucrose was intact in DAT-CI mice, indicating normal sweet perception in these animals. Our results point to CB1Rs as novel molecular players in ADHD, and suggest that therapeutic strategies aimed at interfering with the ECS might prove effective in this disorder.<br /> (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)
- Subjects :
- Animals
Attention Deficit Disorder with Hyperactivity genetics
Attention Deficit Disorder with Hyperactivity physiopathology
Cocaine administration & dosage
Disease Models, Animal
Dopamine Uptake Inhibitors administration & dosage
Dronabinol analogs & derivatives
Dronabinol pharmacology
Excitatory Amino Acid Antagonists pharmacology
Food Preferences physiology
Gene Expression Regulation genetics
In Vitro Techniques
Inhibitory Postsynaptic Potentials genetics
Male
Methoxyhydroxyphenylglycol analogs & derivatives
Methoxyhydroxyphenylglycol pharmacology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Motor Activity genetics
Receptor, Cannabinoid, CB1 genetics
Receptors, GABA-B metabolism
Sucrose administration & dosage
Attention Deficit Disorder with Hyperactivity pathology
Corpus Striatum metabolism
Dopamine Plasma Membrane Transport Proteins genetics
Point Mutation genetics
Receptor, Cannabinoid, CB1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-9568
- Volume :
- 34
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The European journal of neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 22034972
- Full Text :
- https://doi.org/10.1111/j.1460-9568.2011.07876.x