Decreased Nucleus Accumbens Expression of Psychiatric Disorder Risk Gene Cacna1c Promotes Susceptibility to Social Stress.
Polymorphisms in the CACNA1C gene are associated with human mood disorders. The rodent social defeat model of stress/mood-disorder susceptibility results in maladaptive consequences mediated by altered function of mesolimbic circuits.



mRNA levels of Cacna1c in the nucleus accumbens of mice exposed to social defeat were assessed. Cacna1c was selectively deleted in the nucleus accumbens of floxed Cacna1c mice using viral Cre-recombinase to examine Cacna1c in social defeat susceptibility.



Reduced expression of Cacan1c in the nucleus accumbens is associated with increased susceptibility to social defeat stress, and a knockdown of Cacna1c in the nucleus accumbens significantly increases susceptibility measured by social interaction and female urine preference.



Cacna1c reduction causally predisposes to the maladaptive outcomes of social stress. Normal Cacna1c function in the nucleus accumbens is crucial for resiliency to social stressors. Variations in expression of CACNA1C in the nucleus accumbens may mediate human risk for developing mood disorders and be a target for therapeutic intervention.
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Chantelle E
CE
Terrillion
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland, USA.
T Chase
TC
Francis
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Adam C
AC
Puche
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Mary Kay
MK
Lobo
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Todd D
TD
Gould
D000818:Animals; D001007:Anxiety / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000378:metabolism*; D012903:Smell / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics* / Q000473:pathology*; D014161:Transduction, Genetic
C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D049452:Green Fluorescent Proteins
CACNA1C; bipolar disorder; depression; genetics; nucleus accumbens