6.1.2. Dopamine

Dopamine is a neurotransmitter important in reward processing, produced mainly in the areas of the brain implicated in reward, such as the substantia nigra and ventral tegmental area. Reward constitutes three main processes: "liking" (a hedonic impact), "wanting" (incentive salience) and learning (habit formation and forming associations) [106]. Whilst dopamine is implicated in all reward processes, studies suggest that it is most important for "wanting" processes [107,108] and, thus, is a large feature in theories of addiction.

In AN, alterations in the dopaminergic reward system have been noted, although the findings are complex and often contradictory [109]. Overall, the findings suggest that alterations in dopamine in AN may drive difficulties in discriminating between punishment and reward, which is related to increased levels of anxiety and harm avoidance [110]. It has been suggested that AN-related cues and behaviours become rewarding over time, as increases in stress hormones attributable to food restriction can stimulate the dopamine reward system via the hypothalamic–pituitary–adrenal axis [111]. Repeated dopamine signalling may then aid in the transfer of these behaviours into habits [111,112]. Thus, it has been suggested that treatments focus on developing associations with recovery goals and egosyntonic aspects of the disorder rather than simply on food cues [110]. However, this is likely to be especially difficult in patients who remain underweight or have the treatment-resistant form of AN, as poor engagement in therapies and cognitive difficulties may interfere.

Ketamine has been found to modulate the brain circuits related to reward and motivation [113,114]. For example, resting-state functional magnetic resonance imaging (MRI) scans of patients with treatment-resistant depression two days post-ketamine infusion demonstrated increases in the frontostriatal connectivity in one study [115]. An additional study provided evidence for increases in synaptic plasticity in the hippocampus–accumbens pathway, which occurred partially due to the activation of D1 receptors [116]. Thus, it is possible that using the suggested psychological approaches above within a window of ketamine-induced neuroplasticity may instigate changes in reward functioning and reward-related associations with disordered cues.
