Decreased Nucleus Accumbens Expression of Psychiatric Disorder Risk Gene Cacna1c Promotes Susceptibility to Social Stress

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.