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AMPA receptor antagonism attenuates MK-801-induced hypermetabolism in the posterior cingulate cortex
1Wellcome Surgical Institute and Hugh Fraser Neuroscience Laboratories, University of Glasgow, UK.
Abstract:
The effect of pretreatment with an AMPA receptor antagonist, NBQX, on MK-801-induced alterations in glucose use was examined using [14C]-2-deoxyglucose autoradiography. NBQX (7 mg/kg) had minimal effect on glucose utilisation in all anatomical regions examined. The intravenous administration of MK-801 (0.2 mg/kg) induced increases in glucose use in the limbic system and cingulate cortex. MK-801 reduced glucose utilisation in the sensory motor and auditory cortices. Pretreatment with NBQX attenuated the MK-801-induced hypermetabolism in the posterior cingulate cortex. The decreases in glucose utilisation induced by MK-801 were not exacerbated by the pretreatment with NBQX. The interaction between NBQX and MK-801 suggests a possible method of attenuating some of the adverse effects of the non-competitive NMDA receptor antagonists in the posterior cingulate cortex.
Insights
This study investigated how NBQX, an AMPA receptor antagonist, affects MK-801
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Non-competitive NMDA receptor antagonists like MK-801 can cause significant alterations in brain glucose metabolism.
- AMPA receptors play a role in modulating neuronal activity and may influence the effects of NMDA receptor antagonists.
Purpose of the Study:
- To investigate the effect of NBQX, an AMPA receptor antagonist, on MK-801-induced changes in brain glucose utilization.
- To determine if NBQX can mitigate adverse effects associated with MK-801 administration.
Main Methods:
- Utilized [14C]-2-deoxyglucose autoradiography in animal models.
- Examined the impact of NBQX (7 mg/kg) and MK-801 (0.2 mg/kg) administration, both individually and in combination, on regional brain glucose metabolism.
Main Results:
- MK-801 increased glucose utilization in the limbic system and cingulate cortex, while decreasing it in sensory motor and auditory cortices.
- NBQX pretreatment attenuated MK-801-induced hypermetabolism specifically in the posterior cingulate cortex.
- NBQX did not worsen MK-801-induced hypometabolism in other brain regions.
Conclusions:
- Co-administration of NBQX with MK-801 can selectively attenuate hypermetabolic effects in the posterior cingulate cortex.
- This interaction suggests a potential strategy for mitigating adverse effects of non-competitive NMDA receptor antagonists.