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Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats

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Abstract

Rationale

Metabotropic glutamate receptors (mGluRs) were reported to regulate various behavioral effects of addictive drugs.

Objective

The present study evaluated the role of group I mGluRs in the progressive augmentation (“sensitization”) of the behavioral effects observed after repeated, intermittent cocaine exposure.

Materials and methods

After habituation to handling and baseline activity measurement (days 1–2), rats received eight injections of cocaine (10 mg/kg) or saline on days 3–6, 8–11, and then, were tested twice with acute saline and cocaine given in a counterbalanced manner on days 13 and 15. Before the test sessions, subjects were pretreated with mGluR1 antagonist EMQMCM (JNJ16567083, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine).

Results

Pretreatment with EMQMCM (2.5–10 mg/kg) but not MTEP (2.5–10 mg/kg) significantly reduced expression of the sensitized ambulatory motor activity of the cocaine-experienced animals acutely challenged with cocaine. Both EMQMCM and MTEP significantly reduced vertical motor activity across all cocaine/saline treatment conditions.

Conclusions

These findings indicate that the expression of behavioral sensitization to cocaine-induced stimulation of locomotor activity may be modulated by group I mGluR antagonists (mGluR1 rather than mGluR5), but these effects occur at the dose levels that attenuate vertical activity.

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Acknowledgements

Supported in part by the Fogarty International Research Collaboration Award # R03TW00714. The authors are grateful to Vladimir Kashkin for the excellent technical assistance.

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Author notes

  1. Anton Y. Bespalov

    Present address: CNS Pharmacology, Abbott GmbH & Co. KG, 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 Lev Tolstoy Street, St. Petersburg, 197089, Russia

    Olga A. Dravolina & Anton Y. Bespalov

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

    Wojciech Danysz

Authors
  1. Olga A. Dravolina
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  2. Wojciech Danysz
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Correspondence to Olga A. Dravolina.

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Dravolina, O.A., Danysz, W. & Bespalov, A.Y. Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats. Psychopharmacology 187, 397–404 (2006). https://doi.org/10.1007/s00213-006-0440-1

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