HAB Mice Displayed Behavioral Insensitivity to SSRIs
To investigate whether the HAB mouse model mimics features of treatment resistance, we first examined the efficacy of different classes of antidepressant drugs in reducing the enhanced depression-like behavior displayed by HAB mice in comparison with NAB mice. Reproducing our previous results (Sah et al, 2012), the immobility displayed in the FST was enhanced in HAB animals compared with their NAB counterparts. Chronic treatment with one of three SSRIs did not change the high immobility scores of male HAB mice in the FST (F4,31=156.8, P<0.001; Figure 1). We observed that treatment resistance seemed to be restricted to drugs targeting solely the serotonergic system, as both the selective noradrenaline re-uptake inhibitor reboxetine and the tricyclic antidepressant desipramine significantly reduced the depression-like behavior of HAB mice assessed in the FST (F2,22=8.761, P=0.002) (Supplementary Figure S1).