Interaction between the mGlu receptors 5 antagonist, MPEP, and amphetamine on memory and motor functions in mice

Metabotropic glutamate mGlu receptors 5 (mGluR5) receptors are abundant in corticolimbic circuitry where they modulate glutamate and dopamine signal transduction. In this study, we explored the hypothesis that mGluR5 antagonist, (2-methyl-6-(phenylethynyl)pyridine hydrochloride) (MPEP), facilitates dopamine-dependent effects on memory and motor functions. To this aim, we examined the effects of different doses (from 0 to 24 mg/kg) of the mGluR5 antagonist, MPEP, on the modulation of amphetamine-dependent behaviors, namely passive avoidance, locomotor activity, and rotation behavior in intact and dopamine-depleted CD1 male mice. We demonstrated that a low dose (3 mg/kg) of MPEP, which is void of behavioral effects on its own, facilitates amphetamine-induced effects independently on the behavior measured both in na < ve and in dopamine-lesioned mice; this synergistic effect is lost when higher doses of MPEP are used. The results are discussed in terms of possible balance between dopamine and glutamate activity in regulating the proper fine tuning of information processing.