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Adenosine A2A receptor antagonism reverses the effects of dopamine receptor antagonism on instrumental output and effort-related choice in the rat: implications for studies of psychomotor slowing

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Abstract

Rationale

Organisms frequently make effort-related decisions based upon assessments of motivational value and response costs. Energy-related dysfunctions such as psychomotor slowing and apathy are critically involved in some clinical syndromes. Dopamine (DA), particularly in the nucleus accumbens, regulates effort-related processes. Dopamine antagonism and accumbens dopamine depletions cause rats performing on choice tasks to reallocate their behavior away from food-reinforced tasks that have high response requirements.

Objective

There is evidence of a functional interaction between DA and adenosine A2A receptors in the neostriatum and nucleus accumbens. The present experiments were conducted to determine if adenosine A2A receptor antagonism could reverse the effects of dopamine receptor antagonism on instrumental behavior and effort-related choice.

Materials and methods

The adenosine A2A receptor antagonist MSX-3 was investigated for its ability to reverse the effects of the dopamine receptor antagonist haloperidol (0.1 mg/kg) on fixed ratio 5 instrumental lever-pressing and on response allocation using a concurrent lever-pressing/chow-feeding choice task.

Results

Haloperidol significantly suppressed fixed ratio 5 responding, and with rats responding on the concurrent choice task, it altered choice behavior, significantly reducing lever-pressing for food and increasing chow intake. Injections of MSX-3 (0.5–2.0 mg/kg) produced a dose-related attenuation of the effects of 0.1 mg/kg haloperidol on both tasks. The high dose of MSX-3, when administered in the absence of haloperidol, did not significantly affect responding on either task.

Conclusions

Adenosine and dopamine systems interact to regulate instrumental behavior and effort-related processes, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing or anergia.

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Acknowledgements

This research was supported by a grant to JDS from the United States NIH/NINDS. Many thanks to Keita Ishiwari for his technical assistance.

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Authors and Affiliations

  1. Department of Psychology, University of Connecticut, Storrs, CT, 06269-1020, USA

    Andrew M. Farrar & John D. Salamone

  2. Pharmazeutisches Institut, Universität Bonn, Pharmazeutische Chemie, Poppelsdorf, Bonn, Germany

    Jörg Hockemeyer & Christa E. Müller

  3. Seccion Fisiologia y Nutricion, Facultad de Ciencias, Universidad de la Republica, Montevideo, Uruguay

    Mariana Pereira

  4. University of Guadalajara, Guadalajara, Mexico

    Francisco Velasco

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  1. Andrew M. Farrar
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  2. Mariana Pereira
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  3. Francisco Velasco
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  4. Jörg Hockemeyer
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  5. Christa E. Müller
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  6. John D. Salamone
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Correspondence to John D. Salamone.

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Farrar, A.M., Pereira, M., Velasco, F. et al. Adenosine A2A receptor antagonism reverses the effects of dopamine receptor antagonism on instrumental output and effort-related choice in the rat: implications for studies of psychomotor slowing. Psychopharmacology 191, 579–586 (2007). https://doi.org/10.1007/s00213-006-0554-5

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  • DOI: https://doi.org/10.1007/s00213-006-0554-5

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