SDPS proneness was accompanied by heightened reactivity to alcohol‐signifying cues and promoted reinstatement of alcohol seeking, a common characteristic of animals displaying dependence‐like behaviors30 and in SDPS‐induced chronic depression.20 In accordance with the effect of SDPS susceptibility in time‐out responding, aggravated relapse could reflect reduced cognitive control, ie, an inability in refraining from alcohol seeking and alcohol taking. This notion is supported by our observations that guanfacine pretreatment normalized heightened alcohol seeking in the SDPS‐prone animals during reinstatement. Dysfunctional inhibitory control toward alcohol has been observed before in mice that, similar to the SDPS‐prone group, show preference for alcohol.39 Likewise, mice selected for decreased inhibitory control show escalated motivation for alcohol, increased time‐out responding, and enhanced relapse following presentation of alcohol signifying cues,44 three phenotypes present in the SDPS‐prone population. It is possible that these deficits are exaggerated by dysregulation of the brain's reward system, which is present in the depression susceptible but not in the unsusceptible subpopulation,15 leading to maladaptive responsivity to alcohol‐paired cues.
