50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gather the vast evidence for a role of dopamine in the simplest form of aversive learning: passive aversive conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine in order to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic, and optogenetic approaches now provide causal evidence for dopamine’s role in these learning processes. Dopamine neurons encode fear and extinction-related information and convey the signal via activation of D1, D2, D3, and D4 receptor sites particularly in the amygdala, prefrontal cortex, and striatum in order to continuously form, consolidate, retrieve, and update fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of passive aversive conditioning and contributes in a way that is comparable to its role in encoding reward.