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Reduction of corticostriatal glutamatergic fibers in basic fibroblast growth factor deficient mice is associated with hyperactivity and enhanced dopaminergic transmission.
- Source :
-
Biological psychiatry [Biol Psychiatry] 2007 Aug 01; Vol. 62 (3), pp. 235-42. Date of Electronic Publication: 2006 Dec 08. - Publication Year :
- 2007
-
Abstract
- Background: Basic fibroblast growth factor (FGF2) plays a crucial role during the development of the cerebral cortex. Mice with a knockout of the FGF2 gene have a reduced number of glutamatergic neurons within the deep layers of the cerebral cortex.<br />Methods: We used molecular and behavioral analyses to investigate possible alterations in corticostriatal function in FGF2 -/- mice.<br />Results: We found that FGF2 deficiency leads to decreased expression of presynaptic markers of integrity for glutamatergic fibers in the striatum, namely the membrane excitatory amino acid transporter 3 (EAAT3) and the vesicular glutamate transporter 1 (VGLUT1). The reduction of corticostriatal glutamatergic function in FGF2 -/- mice is associated with enhanced locomotor activity in a novel environment and increased responsiveness to dopaminergic drugs, such as cocaine or amphetamine. The behavioral alterations of FGF2 -/- can be normalized by injection of a low dose of the dopaminergic agonist apomorphine (.1 mg/kg) that reduces dopamine release by acting on presynaptic receptors.<br />Conclusions: Our data demonstrate that FGF2 -/- mice have an increased tone and responsiveness of the dopaminergic system and suggest that these animals might represent a model to study disorders that are characterized by an imbalance between glutamatergic and dopaminergic neurotransmission.
- Subjects :
- Actins genetics
Actins metabolism
Analysis of Variance
Animals
Apomorphine pharmacology
Cocaine pharmacology
Dextroamphetamine pharmacology
Dopamine Agents pharmacology
Excitatory Amino Acid Transporter 3 genetics
Excitatory Amino Acid Transporter 3 metabolism
Exploratory Behavior drug effects
Exploratory Behavior physiology
Fibroblast Growth Factor 2 deficiency
Frontal Lobe cytology
Frontal Lobe drug effects
Glutamic Acid metabolism
Hyperkinesis metabolism
Mice
Mice, Knockout
Motor Activity drug effects
Neostriatum drug effects
Nerve Fibers metabolism
Presynaptic Terminals drug effects
Presynaptic Terminals metabolism
RNA, Messenger analysis
Synaptic Transmission physiology
Vesicular Glutamate Transport Protein 1 genetics
Vesicular Glutamate Transport Protein 1 metabolism
Dopamine metabolism
Fibroblast Growth Factor 2 physiology
Frontal Lobe metabolism
Motor Activity physiology
Neostriatum metabolism
Neural Pathways metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3223
- Volume :
- 62
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biological psychiatry
- Publication Type :
- Academic Journal
- Accession number :
- 17161387
- Full Text :
- https://doi.org/10.1016/j.biopsych.2006.08.003