The role of adenosine in the ventral striatal circuits regulating behavioral activation and effort-related decision making: Importance for normal and pathological aspects of motivation

Motivated behavior can be characterized by a high degree of activity, vigor, and persistence. Brain dopamine (DA), particularly in the nucleus accumbens, has been implicated in activational aspects of motivation and effort-related processes. Accumbens DA 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 A_2A receptors, also participates in regulating effort-related processes. Intra-accumbens injections of adenosine A_2A agonists produce effects that are similar to those produced by accumbens DA depletion or antagonism. Furthermore, systemic or intra-accumbens injections of adenosine A_2A receptor antagonists can reverse the effects of DA D₂ antagonists on effort-related choice behavior. In contrast, adenosine A₁ receptor antagonists fail to reverse these motivational effects of DA D₂ antagonism. These studies have implications for understanding the potential role of adenosine in the development and treatment of energy-related motivational symptoms such as anergia and fatigue in depression and other disorders.