Related Experiment Video
Updated: Aug 25, 2026
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats
Una C Campbell1, Kush Lalwani, Lisa Hernandez
1Department of Pharmacology, Merck Research Laboratories, San Diego, CA 92121, USA una_campbell@merck.com
Rationale:
Recent studies have shown that metabotropic glutamate receptor 5 (mGluR5) can modulate N-methyl-D-aspartate (NMDA) receptor function in vivo. For example, the mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) can potentiate PCP (phencyclidine)-evoked hyperactivity and PCP-induced disruptions in pre-pulse inhibition (PPI) in rats.
Objective:
To extend these previous behavioral findings and determine whether the mGluR5 antagonist MPEP can modulate the disruptions in learning and memory induced by PCP in rats.
Methods:
The effects of MPEP, alone and in combination with PCP, were evaluated in rats trained to perform a repeated acquisition procedure (learning) or a delayed non-matching to position (DNMTP) radial maze task (spatial memory).
Results:
In the repeated acquisition task, MPEP (0-10 mg/kg, IP) dose-dependently decreased response rates but had no effect on response accuracy. In contrast, PCP (0.625-1.25 mg/kg, SC) reduced response rate and response accuracy in a dose-dependent manner. Although MPEP (10 mg/kg, IP) had no effect when administered alone, the mGluR5 antagonist potentiated the disruptions in learning induced by a low dose of PCP (0.625 mg/kg, SC). In the DNMTP maze task, MPEP (0-10 mg/kg, IP) had no effect on spatial memory, whereas PCP (1.25-2.5 mg/kg, SC) produced a dose-dependent disruption. MPEP (10 mg/kg, IP) potentiated the impairments in memory induced by PCP (1.25 mg/kg, SC).
Conclusion:
The mGluR5 antagonist, MPEP, potentiated the disruptions in learning and memory induced by PCP. These behavioral data extend previous behavioral findings and further suggest that mGluR5 can modulate NMDA receptor function in vivo.
Insights
The metabotropic glutamate receptor 5 (mGluR5) antagonist MPEP worsened phencyclidine (PCP)-induced learning and memory deficits in rats. This suggests mGluR5 plays a role in modulating NMDA receptor function.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Metabotropic glutamate receptor 5 (mGluR5) antagonists, like MPEP, are known to modulate N-methyl-D-aspartate (NMDA) receptor function.
- Previous research indicates MPEP can potentiate phencyclidine (PCP)-induced hyperactivity and disruptions in pre-pulse inhibition in rats.
Purpose of the Study:
- To investigate the effect of the mGluR5 antagonist MPEP on PCP-induced learning and memory impairments in rats.
- To determine if mGluR5 modulates NMDA receptor-mediated cognitive deficits.
Main Methods:
- Rats were trained on a repeated acquisition task (learning) and a delayed non-matching to position (DNMTP) radial maze task (spatial memory).
- The effects of MPEP, alone and in combination with PCP, were evaluated on these tasks.
Main Results:
- MPEP alone did not affect learning or memory accuracy but decreased response rates.
- PCP impaired both learning and memory in a dose-dependent manner.
- MPEP potentiated PCP-induced deficits in both learning and spatial memory.
Conclusions:
- The mGluR5 antagonist MPEP exacerbates PCP-induced impairments in learning and memory.
- These findings support the role of mGluR5 in modulating NMDA receptor function in vivo.
