Whereas contemporary neuroimaging evidence supports a role for dysfunctioning prefrontal-amygdaloid-striatal circuitry in affective disorders, precise psychological functions of this interaction have still to be revealed, thus providing barriers to producing new treatments for these debilitating conditions. The great advantage of murine models of psychiatric disorders is the availability of the novel neuroscience tools, including optogenetics and designer receptors exclusively activated by designer drugs (DREADDs), which enable the molecular features of specific functional circuits identified in human neuroimaging studies to be further characterized and novel molecular targets for drug discovery to be identified.