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Interaction between the mGlu receptors 5 antagonist, MPEP, and amphetamine on memory and motor functions in mice
Francesca Managò1, Sebastien Lopez, Alberto Oliverio
1Dipartimento di Biologia e Biotecnologie "C. Darwin", Università degli Studi di Roma "La Sapienza", Rome, Italy.
Rationale:
Metabotropic glutamate mGlu receptors 5 (mGluR5) receptors are abundant in corticolimbic circuitry where they modulate glutamate and dopamine signal transduction.
Objectives:
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.
Methods:
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.
Results:
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 naïve and in dopamine-lesioned mice; this synergistic effect is lost when higher doses of MPEP are used.
Conclusion:
The results are discussed in terms of possible balance between dopamine and glutamate activity in regulating the proper fine tuning of information processing.
Insights
A low dose of the metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP enhances amphetamine-induced memory and motor functions. Higher MPEP doses diminish these dopamine-related effects.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Metabotropic glutamate mGlu receptors 5 (mGluR5) are key in corticolimbic circuits, regulating glutamate and dopamine signaling.
- Dysregulation of these pathways is implicated in various neurological and psychiatric conditions.
Purpose of the Study:
- To investigate if the mGluR5 antagonist MPEP potentiates dopamine-dependent memory and motor functions.
- To explore the dose-dependent effects of MPEP on amphetamine-induced behaviors.
Main Methods:
- Examined effects of MPEP (0-24 mg/kg) on amphetamine-induced passive avoidance, locomotor activity, and rotation behavior.
- Utilized intact and dopamine-depleted CD1 male mice models.
Main Results:
- A low MPEP dose (3 mg/kg) facilitated amphetamine effects on all measured behaviors in both intact and dopamine-depleted mice.
- This synergistic effect was dose-dependent, with higher MPEP doses showing no facilitation.
Conclusions:
- Suggests a potential balance between dopamine and glutamate activity in information processing.
- MPEP at low doses may modulate dopaminergic neurotransmission, impacting cognitive and motor functions.
