Differential effects of selective adenosine antagonists on the effort-related impairments induced by dopamine D1 and D2 antagonism
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Otros documentos de la autoría: Nunes, Eric J.; Randall, Patrick A.; Santerre, Jessica L.; Given, A. B.; Sager, Thomas Nikolaj; Correa, Merce; Salamone, John
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http://dx.doi.org/10.1016/j.neuroscience.2010.05.068 |
Metadatos
Título
Differential effects of selective adenosine antagonists on the effort-related impairments induced by dopamine D1 and D2 antagonismAutoría
Fecha de publicación
2010Editor
ElsevierISSN
3064522Cita bibliográfica
Neuroscience, 170, 1, p. 268-280Tipo de documento
info:eu-repo/semantics/articleVersión
info:eu-repo/semantics/publishedVersionPalabras clave / Materias
Resumen
Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away ... [+]
Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. Previous work showed that adenosine A<sub>2A</sub> antagonists can reverse the effects of DA D<sub>2</sub> antagonists on effort-related choice. However, less is known about the effects of adenosine A<sub>1</sub> antagonists. Despite anatomical data showing that A<sub>1</sub> and D<sub>1</sub> receptors are co-localized on the same striatal neurons, it is uncertain if A<sub>1</sub> antagonists can reverse the effects DA D<sub>1</sub> antagonists. The present work systematically compared the ability of adenosine A<sub>1</sub> and A<sub>2A</sub> receptor antagonists to reverse the effects of DA D<sub>1</sub> and D<sub>2</sub> antagonists on a concurrent lever pressing/feeding choice task. With this procedure, rats can choose between responding on a fixed ratio 5 lever-pressing schedule for a highly preferred food (i.e. high carbohydrate pellets) vs. approaching and consuming a less preferred rodent chow. The D<sub>1</sub> antagonist ecopipam (0.2 mg/kg i.p.) and the D<sub>2</sub> antagonist eticlopride (0.08 mg/kg i.p.) altered choice behavior, reducing lever pressing and increasing lab chow intake. Co-administration of the adenosine A<sub>1</sub> receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.375, 0.75, and 1.5 mg/kg i.p.), and 8-cyclopentyltheophylline (CPT; 3.0, 6.0, 12.0 mg/kg i.p.) failed to reverse the effects of either the D<sub>1</sub> or D<sub>2</sub> antagonist. In contrast, the adenosine A<sub>2A</sub> antagonist KW-6002 (0.125, 0.25 and 0.5 mg/kg i.p.) was able to produce a robust reversal of the effects of eticlopride, as well as a mild partial reversal of the effects of ecopipam. Adenosine A<sub>2A</sub> and DA D<sub>2</sub> receptors interact to regulate effort-related choice behavior, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, fatigue or anergia that can be observed in depression and other disorders. © 2010 IBRO. [-]
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