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Differential effects of the adenosine A2A agonist CGS-21680 and haloperidol on food-reinforced fixed ratio responding in the rat

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Abstract

Rationale

Previous studies have shown that adenosine A2A receptors are colocalized with dopamine D2 receptors on striatal neurons. Activation of these two receptors has antagonistic effects under a number of conditions suggesting that stimulation of adenosine A2A receptors may have behavioral effects resembling those produced by blockade of dopamine D2 receptors, but this possibility has been investigated in a limited number of situations.

Objective

We compared the effects of the adenosine A2A agonist CGS-21680 and the preferential D2 dopamine antagonist haloperidol in a situation in which dopamine blockade produces a distinctive pattern of behavioral effects.

Materials and methods

Six rats were trained to lever press for food reward on a fixed ratio 15 schedule of reinforcement and then tested after being injected with various doses of CGS-21680 (0.064, 0.128, and 0.25 mg/kg) and haloperidol (0.25 and 0.1 mg/kg).

Results

Haloperidol produced a dose-dependent suppression of lever pressing with mean response rates declining across the duration of the test session. CGS-21680 also produced a dose-dependent suppression of responding, but this effect was not temporally graded, and responding was equivalently suppressed across the duration of the session. Additionally, CGS-21680 increased post-reinforcement pause duration to a much greater extent than did haloperidol.

Conclusions

On this task, the behavioral effects of CGS-21680 do not resemble those produced by haloperidol. Several explanations of this discrepancy are possible, the most likely being that the observed behavioral effects of CGS-21680 result from an action at a site other than D2 receptor-expressing striatal neurons.

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Acknowledgments

This publication is based upon work supported by grants 0641943 from the National Science Foundation, R01DK071738 from the National Institute of Diabetes and Digestive and Kidney Diseases, and R03DA020802 from the National Institute for Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Science Foundation or the National Institutes of Health.

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Authors and Affiliations

  1. College of the Desert, 43-500 Monterey Avenue, Palm Desert, CA, 92260, USA

    Chris Jones-Cage

  2. Laboratory of Integrative Neuroscience and Department of Psychology (M/C 285), University of Illinois at Chicago, 1007 W. Harrison St., Chicago, IL, 60607-7137, USA

    Thomas R. Stratford & David Wirtshafter

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  1. Chris Jones-Cage
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  2. Thomas R. Stratford
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  3. David Wirtshafter
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Correspondence to David Wirtshafter.

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Jones-Cage, C., Stratford, T.R. & Wirtshafter, D. Differential effects of the adenosine A2A agonist CGS-21680 and haloperidol on food-reinforced fixed ratio responding in the rat. Psychopharmacology 220, 205–213 (2012). https://doi.org/10.1007/s00213-011-2467-1

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