Selective effects of dorsal raphé nucleus glucocorticoid receptor deletion on depression-like behavior in female C57BL/6J mice.

We have shown differing effects of glucocorticoid receptor (GR) deletion from the dorsal raphé nucleus (DRN) and locus coeruleus (LC) on depression-relevant behavior in male mice, but DRN GR deletion has not been tested in female mice. Female floxed GR mice were given DRN injections of AAV2/9 pseudotype viral vectors transducing Cre recombinase to produce DRN GR gene deletion (Cre) and compared with mice receiving DRN injections of AAV2/9 transducing green fluorescent protein (GFP). Social interaction, a measure of depression-like withdrawal, was unaffected by DRN GR deletion, but forced swim immobility, a measure of despair-like passivity, was reduced in female Cre vs. GFP mice. Behavioral effects were not attributable to changes in basal corticosterone or LC GR deletion. Combined with our prior studies, the current findings suggest that DRN GR have sex-independent effects to promote forced swim immobility, but influence social interaction only in male mice. Differential effects of DRN GR deletion in female mice may provide insight into the greater incidence of depression and specific depression symptoms in women.