Constitutive hyperdopaminergia is functionally associated with reduced behavioral lateralization.
According to the dopamine (DA) hypothesis of schizophrenia and the strong evidence for decreased cerebral lateralization in schizophrenic patients, we postulated that hyperactivity of the dopaminergic system could be associated with a reduced behavioral lateralization in mice. Mice lacking the dopamine transporter (DAT) gene were used as a genetic model of persistent hyperdopaminergia. The DAT null mutation was transferred on C57BL/6JOrl (B6) and DBA/2JOrl (D2) inbred backgrounds for more than 10 generations of backcrossing to derive three DAT strains, B6, D2, and B6xD2(F1). Adult mutant mice of the three DAT strains and their littermates were tested for paw preference using Collins' protocol. Our results demonstrated that, whatever the genetic background, persistent hyperdopaminergia directly impairs the degree of lateralization without affecting the direction. Our results support the degree of lateralization as a good candidate phenotype to further improve genetic analysis of cerebral lateralization in normal and pathological conditions.
Morice
Elise
E
INSERM-U513, Neurobiologie et Psychiatrie, Créteil Cedex, France.
Denis
Cécile
C
Macario
Alessandro
A
Giros
Bruno
B
Nosten-Bertrand
Marika
M
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D007839:Functional Laterality; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics*; D001523:Mental Disorders / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics*; D011930:Reaction Time; D013997:Time Factors
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493215:Slc6a3 protein, mouse; D003042:Cocaine; D004298:Dopamine