Reduction of corticostriatal glutamatergic fibers in basic fibroblast growth factor deficient mice is associated with hyperactivity and enhanced dopaminergic transmission.
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.


METHODS
We used molecular and behavioral analyses to investigate possible alterations in corticostriatal function in FGF2 -/- mice.


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.


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.
Fadda
Paola
P
Department of Neuroscience B.B. Brodie, Center for Excellence in Neurobiology of Dependence, University of Cagliari, Cittadella Universitaria, Monserrato, Italy.
Bedogni
Francesco
F
Fresu
Alessandra
A
Collu
Maria
M
Racagni
Giorgio
G
Riva
Marco A
MA
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency / Q000502:physiology*; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006948:Hyperkinesis / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009412:Nerve Fibers / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D009435:Synaptic Transmission / Q000502:physiology; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000378:metabolism
D000199:Actins; D015259:Dopamine Agents; D050580:Excitatory Amino Acid Transporter 3; D012333:RNA, Messenger; C493399:Slc1a1 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D016222:Fibroblast Growth Factor 2; D018698:Glutamic Acid; D003042:Cocaine; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine