Forebrain neurochemical interactions and circuitry involved in effort-related choice

An enormous body of evidence has demonstrated the importance of nucleus accumbens dopamine (DA) neurotransmission in regulated effort-related processes, including exertion of effort and effort-related choice behavior. Although accumbens DA is a vital component of the brain circuitry regulating effort-related processes, it is recognized that other brain areas and neurotransmitters must also be involved. An emerging body of evidence indicates that striatal DA systems interact with adenosine A2A receptors, and these interactions may also regulate the behavioral functions of the nucleus accumbens. The first three groups of experiments (Chapters 2-4) demonstrated that adenosine A 2A receptor antagonists can reverse the effects of DA antagonism on effort-related choice, and that nucleus accumbens is an important locus for this interaction. The fourth group of experiments (Chapter 5) characterized the anatomical and neurochemical relationship between nucleus accumbens and ventral pallidum (VP), while Chapter 6 focused on the behavioral functions of GABAA receptors in VP. One of the brain areas receiving the greatest input from accumbens is the VP, and the projections from nucleus accumbens to VP are GABAergic. Experiment 5.2 demonstrated that injection of a D2-receptor antagonist in accumbens increased extracellular GABA in VP. On the basis of the results of Chapter 5, it was hypothesized that stimulation of GABAA receptors in the VP would produce behavioral effects on an effort-related choice procedure that closely resemble those produced by interference with accumbens DA transmission. Injections of the GABAA receptor agonist muscimol into VP, but not a dorsal control site, resulted in behavioral effects similar to those produced by interference with accumbens DA transmission. ^ In summary, the present experiments were designed to characterize both the neurochemical and anatomical components of the neural system that underlie effort-related choice. Adenosine A2A receptor antagonists reversed the effects of interference with accumbens DA transmission on effort-related choice behavior, whereas local stimulation of GABAA receptors in VP produced effects that closely resemble those produced by DA antagonists or accumbens DA depletion. The present studies contribute significantly to the characterization of both the neurochemical mechanisms and the anatomical circuitry that are involved in the regulation of effort-related processes.