Effort-related Functions of Nucleus Accumbens Adenosine A2A Receptors

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DESCRIPTION (provided by applicant): The notion that motivated behaviors have an energetic or activational component is a recurring theme in the literatures of psychology and psychiatry. Many researchers have emphasized that the vigor or persistence of work output in stimulus-seeking behavior is a fundamental aspect of motivation. Organisms continually make effort-related decisions based upon cost/benefit analyses, allocating resources into goal- directed behaviors based upon assessments of motivational value and response costs. In the clinical literature, psychiatrists and psychologists have come to emphasize the importance of energy-related dysfunctions, such as psychomotor slowing and apathy, in various clinical syndromes. Because of the scientific importance and clinical relevance of behavioral activation processes, it is critical to investigate the brain mechanisms involved. Considerable evidence indicates that dopamine (DA) in nucleus accumbens regulates behavioral activation processes. The effects of accumbens DA depletions on food-seeking behavior depend greatly upon the work requirements of the task, and interference with accumbens DA transmission exerts a powerful influence over effort-related decision making. Nevertheless, it should be recognized that accumbens DA only functions as one component of the brain circuitry regulating activational aspects of motivation. Mesolimbic DA is embedded into a larger network of neural processes involving other brain areas and transmitters. Evidence indicates that there is a functional interaction between DA and adenosine A2A receptors in striatal areas, including the nucleus accumbens. This interaction typically is studied in the context of animal models related to parkinsonism, but less is known about the effort-related functions of adenosine A2A receptors in nucleus accumbens. Therefore, the proposed experiments will focus upon the effort-related functions of adenosine A2A receptors in the nucleus accumbens. It is hypothesized that blockade of adenosine A2A receptors in nucleus accumbens will reverse the behavioral effects of DA antagonism and accumbens DA depletion, and that local stimulation of adenosine A2A receptors will alter the exertion of effort and effort-related decision making in a manner that is similar to the effects of interference with DA transmission. From a mental health perspective, it is vital to study the role of adenosine A2A receptors in effort-related processes because such studies could provide information about a fundamental aspect of motivation, and also because they could lead to the development of novel treatments for energy-related disorders such as psychomotor slowing in depression, anergia or apathy.