Serotonin transporter, 5-HT1A receptor, and behavior in DBA/2J mice in comparison with four inbred mouse strains.
Prepulse inhibition (PPI), the reduction in acoustic startle produced when it is preceded by a weak prepulse stimulus, is impaired in schizophrenic patients. The DBA/2J mouse strain displayed deficient PPI and is therefore suggested as an experimental animal model for the loss of sensorimotor gating in schizophrenia. Brain serotonin (5-HT) has been implicated in the pathophysiology of several psychiatric disorders, including major depressive disorder and schizophrenia. In the present study, behavior, 5-HT transporter (5-HTT) mRNA level, 5-HT(1A) receptor mRNA level, and 5-HT(1A) receptor density in the brain regions were studied in DBA/2J mice in comparison with four inbred mouse strains (CBA/Lac, C57BL/6, BALB/c, and ICR). A decrease in 5-HTT mRNA level in the midbrain and a reduced density of 5-HT(1A) receptors in the frontal cortex without significant changes in 5-HT(1A) receptor mRNA level in DBA/2J mice were found. It was shown that, along with decreased PPI, DBA/2J mice demonstrated considerably reduced immobility in the tail suspension test and in the forced swim test. No significant interstrain differences in intermale aggression, or in light-dark box and elevated plus-maze tests, were found. The results suggested the involvement of decreased 5-HTT gene expression and 5-HT(1A) receptor density in genetically defined PPI deficiency and showed a lack of any association between PPI deficiency and predisposition to aggressive, anxiety, and depressive-like behaviors.
Popova
Nina K
NK
Department of Behavioral Neurogenomics, Institute of Cytology and Genetics, Siberian Division of Russian Academy of Science, Novosibirsk, Russia.
Naumenko
Vladimir S
VS
Tibeikina
Marina A
MA
Kulikov
Alexander V
AV
D000374:Aggression / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055139:Sensory Gating / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013037:Spatial Behavior / Q000502:physiology; D013045:Species Specificity
D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A