Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Brain dopamine, particularly in the nucleus accumbens, has been implicated in activational aspects of motivation and effort-related processes. Accumbens dopamine depletions reduce the tendency of rats to work for food, and alter effort-related decision making, but leave aspects of food motivation such as appetite intact. Recent evidence indicates that the purine neuromodulator adenosine, largely through actions on adenosine A2A receptors, also participates in regulating effort-related processes. Adenosine A2A antagonists can reverse the effects of dopamine D2 antagonists on effort-related choice, and intra- accumbens injections of adenosine A2A agonists produce effects that are similar to those induced by accumbens dopamine depletion or antagonism. These studies have implications for the understanding and treatment of energy-related disorders such as anergia and fatigue in psychiatry and neurology