Direct dopamine agonists and reuptake inhibitors are not targeted to increase dopamine in respose to particular environmental stimuli, but rather provoke a generally stimulating effect. This is usually undesirable (though often the "lesser of two evils" when compared to no treatment at all!). However, an alternative exists: some receptors act to inhibit or enhance the release of dopamine into the synaptic cleft. In particular, both 5HT2C and KOR activation inhibit dopamine release in brain areas associated with goal-oriented behavior. KOR antagonists are covered extensively in another thread, so I'd like to start a little discussion about 5HT2C here. Unfortunately, at the moment, I can't find the exact paper that most piqued my interest in this direction, but it basically showed that mice who were administered 5HT2C agonists shifted their pattern of activity to low-cost, low-reward strategies, whereas with a 5HT2C inverse agonist, they pursued high-cost, high-reward ones.
Nevertheless, here are several related papers:
However, this effect can be a double-edged sword; hedonic compounds are more enticing with decreased 5HT2C activity:
I believe that a combination of long-acting KOR antagonism + 5HT2C inverse agonism + a balanced amount of dopamine reuptake enhancement (one wants strong dopaminergic pulses, not a steady-state "flood") would be the most effective pharmacological treatment for those (such as myself) who struggle with long-term planning and the pursuit of novel, challenging activities (vs getting stuck in a rut).
