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Effects of mGlu1 receptor blockade on working memory, time estimation, and impulsivity in rats

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Abstract

Rationale

Metabotropic glutamate 1 (mGlu1) receptor antagonists were reported to induce cognitive deficits in several animal models using aversive learning procedures.

Objective

The present study aimed to further characterize behavioral effects of mGlu1 receptor antagonists using appetitively motivated tasks that evaluate working memory, timing, and impulsivity functions.

Materials and methods

Separate groups of adult male Wistar rats were trained to perform four food-reinforced operant tasks: delayed non-matching to position (DNMTP), differential reinforcement of low rates of responding 18 s (DRL 18-s), signal duration discrimination (2-s vs 8-s bisection), and tolerance to delay of reward. Before the tests, rats were pretreated with (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM; 2.5–10 mg/kg, i.p.; JNJ16567083).

Results

In DNMTP task, EMQMCM produced delay-dependent increases in performance accuracy so that, at 10 mg/kg dose level, percentage of correct lever choices was enhanced at 8- and 16-s delays. In DRL task, at all three tested doses, response rates were higher, and reinforcement rates were lower than under control conditions. In signal duration discrimination tasks, EMQMCM did not have any specific effects on temporal control. In tolerance to delay of reward, EMQMCM (5 and 10 mg/kg) facilitated choice of the lever associated with large reward at longer delay levels.

Conclusions

Blockade of mGlu1 receptors improves working memory and reduces impulsive choice at the doses that have no effects on time perception but appear to facilitate impulsive action.

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Acknowledgements

This study was sponsored by Merz Pharmaceuticals.

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Author notes

  1. Anton Y. Bespalov

    Present address: Abbott, Neuroscience Discovery Research, P.O. Box 21 08 05, 67008, Ludwigshafen, Germany

Authors and Affiliations

  1. Laboratory of Behavioral Pharmacology, Institute of Pharmacology, Pavlov Medical University, 6/8 Leo Tolstoy Str., St. Petersburg, 197089, Russia

    Irina A. Sukhotina, Olga A. Dravolina, Yulia Novitskaya, Edwin E. Zvartau & Anton Y. Bespalov

  2. Preclinical R&D, Merz Pharmaceuticals, 100 Eckenheimer Landstrasse, 60318, Frankfurt am Main, Germany

    Wojciech Danysz

Authors
  1. Irina A. Sukhotina
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  2. Olga A. Dravolina
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  3. Yulia Novitskaya
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  4. Edwin E. Zvartau
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  5. Wojciech Danysz
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  6. Anton Y. Bespalov
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Corresponding author

Correspondence to Anton Y. Bespalov.

Additional information

Irina A. Sukhotina and Olga A. Dravolina contributed equally to this manuscript.

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Sukhotina, I.A., Dravolina, O.A., Novitskaya, Y. et al. Effects of mGlu1 receptor blockade on working memory, time estimation, and impulsivity in rats. Psychopharmacology 196, 211–220 (2008). https://doi.org/10.1007/s00213-007-0953-2

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  • DOI: https://doi.org/10.1007/s00213-007-0953-2

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