The pleasure of absent danger.

Anxiety patients have excessive fears that persist despite objective safety. Gradually exposing patients to increasingly feared situations is generally helpful for extinguishing these fears. Recent developments emphasize that expectancy violation is key in exposure: the mismatch between what was expected (danger) and what actually happens (no danger) drives new safety learning that counters the danger expectation. It is increasingly clear that the brain’s dopamine-reward system is activated during omissions of expected danger and underlies the learning of safety. But it remains unclear what triggers this reward system during omissions. How do aversive expectations transform “nothing”, the mere absence of expected danger, into a rewarding event?
We propose a key role for the opioid system, because of its dual role in mitigating pain and producing pleasure: Aversive expectations trigger opioid release pre-emptively to mitigate impending pain, which might result in an overshoot of opioids when the painful stimulation remains absent, and produce pleasure instead.
We will investigate this hypothesis (1) by using fMRI to test whether neural processing of omissions is localized in opioid-rich areas of the brain, (2) by using pharmacological manipulations to test whether neural processing of omissions depends on opioid receptors, and (3) by using molecular imaging (PET) to test whether individual levels of opioid receptor density/activity predict neural processing of omissions.