Constitutive Hyperdopaminergia is Functionally Associated with Reduced Behavioral Lateralization

• Published in: Neuropsychopharmacology Vol. 30; no. 3; pp. 575 - 581
• Main Authors: MORICE, Elise, DENIS, Cécile, MACARIO, Alessandro, GIROS, Bruno, NOSTEN-BERTRAND, Marika
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01.03.2005; Nature Publishing Group
• Subjects: Adult and adolescent clinical studies; Animals; Antipsychotics; Asymmetry; Biological and medical sciences; Cocaine - pharmacology; Cognitive science; Dopamine; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins; Functional Laterality; Handedness; Hyperactivity; Hypotheses; Medical sciences; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Transport Proteins - deficiency; Membrane Transport Proteins - genetics; Mental Disorders - physiopathology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; Mutation; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Neuroscience; Physiology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Psychotropic drugs; Reaction Time; Schizophrenia; Time Factors; Dopamine; Hemispheric specialization; knockout mice; CNS stimulant; Psychotropic; Schizophrenia; Catecholamine; Direction; Paw preference; Psychosis; Local anesthetic; Ester; Asymmetry; Knockout mouse; Neurotransmitter; direction and degree of asymmetry; Cocaine; Drug of abuse; Behavior; Laterality
• ISSN: 0893-133X; 1740-634X; 0007-0920
• DOI: 10.1038/sj.npp.1300570

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.