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Effect of the mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) on the acute locomotor stimulant properties of cocaine, d-amphetamine, and the dopamine reuptake inhibitor GBR12909 in mice

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Abstract

Rationale

Recent evidence suggests that, in addition to ascending monoaminergic systems, glutamate systems also play a role in psychostimulant-induced locomotor activity. The present study was conducted to examine the effects of the selective type-5 metabotropic glutamate receptor (mGluR5) antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) on the acute locomotor stimulant effects of cocaine, d-amphetamine, and the dopamine reuptake inhibitor GBR12909.

Methods

Male DBA/2J mice were treated with saline or MPEP (1, 5, 20 or 30 mg/kg i.p.) 10 min prior to the administration of cocaine (15 mg/kg or 30 mg/kg i.p.), d-amphetamine (3 mg/kg or 5 mg/kg i.p.) or GBR12909 (10 mg/kg or 20 mg/kg i.p.). Locomotor activity was then monitored in an open-field environment for 30 min. The effects of MPEP alone (1, 5, 20 and 30 mg/kg i.p.) on locomotor activity were also examined.

Results

MPEP dose dependently inhibited the acute locomotor stimulant effects of cocaine, d-amphetamine, and the 10-mg/kg dose of GBR12909. However, MPEP had no effect on the locomotor stimulant effects of the higher (20 mg/kg) dose of GBR12909. When tested alone, MPEP increased locomotor activity at doses of 5 mg/kg and 20 mg/kg.

Conclusions

Our data suggest that mGluR5 receptors not only mediate spontaneous locomotor activity in DBA/2J mice but also the acute locomotor stimulant effects of cocaine, d-amphetamine and lower doses of GBR12909. However, the fact that MPEP did not attenuate the locomotor stimulant effects of the high (20 mg/kg) dose of GBR12909 suggests complex interactions between metabotropic glutamate receptors, dopamine transporters and possibly other monoamines in the regulation of psychostimulant-induced locomotor activity.

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Acknowledgements

This work was supported by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California at San Francisco.

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  1. Department of Neurology, Ernest Gallo Clinic and Research Center, University of California at San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA

    Andrew J. Mcgeehan, Patricia H. Janak & M. Foster Olive

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Mcgeehan, A.J., Janak, P.H. & Olive, M.F. Effect of the mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP) on the acute locomotor stimulant properties of cocaine, d-amphetamine, and the dopamine reuptake inhibitor GBR12909 in mice. Psychopharmacology 174, 266–273 (2004). https://doi.org/10.1007/s00213-003-1733-2

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