Nucleus Accumbens Adenosine A2A Receptors Regulate Exertion of Effort by Acting on the Ventral Striatopallidal Pathway
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Otros documentos de la autoría: Font Hurtado, Laura; Mingote, Susana; Farrar, Andrew M.; Vontell, Regina; Worden, Lila T.; Stopper, Colin M.; Port, Russell G.; Sink, Kelly S.; Bunce, Jamie G.; Chrobak, James; Salamone, John
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Título
Nucleus Accumbens Adenosine A2A Receptors Regulate Exertion of Effort by Acting on the Ventral Striatopallidal PathwayAutoría
Fecha de publicación
2008Editor
Society for NeuroscienceISSN
02706474Tipo de documento
info:eu-repo/semantics/articleVersión
info:eu-repo/semantics/acceptedVersionPalabras clave / Materias
Resumen
Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the
exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus ... [+]
Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the
exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine
A2A receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A2A receptor agonist CGS 21680
[2-p-(2-carboxyethyl) phenethylamino-5 -N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A2A
receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio
requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens
neurons that project to the ventral pallidum showed adenosineA2A receptors immunoreactivity. Moreover, activation of accumbens
A2A receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral
injections of CGS 21680 into the accumbens and the GABAA agonist muscimol into ventral pallidum (i.e., “disconnection” methods) also
impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus,
accumbens adenosine A2A receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of
the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding
of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression [-]
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