Dopamine Is Necessary for Cue-Dependent Fear Conditioning

Dopamine (DA) is implicated in many behaviors, including motor function, cognition, and reward processing; however, the role of DA in fear processing remains equivocal. To examine the role of DA in fear-related learning, dopamine-deficient (DD) mice were tested in a fear-potentiated startle paradigm. DA synthesis can be restored in DD mice through administration of 3, 4-dihydroxy-l-phenylalanine (l-Dopa), thereby permitting the assessment of fear processing in either a DA-depleted or -replete state. Fear-potentiated startle was absent in DD mice but could be restored by l-Dopa administration immediately after fear conditioning. Selective viral-mediated restoration of DA synthesis within the ventral tegmental area fully restored fear learning in DD mice, and restoration of DA synthesis to DA neurons projecting to the basolateral amygdala restored short-term memory but not long-term memory or shock sensitization. We also demonstrate that the DA D(1) receptor (D(1)R) and D(2)-like receptors are necessary for cue-dependent fear learning. These findings indicate that DA acting on multiple receptor subtypes within multiple target regions facilitates the stabilization of fear memory.