ArticlePhysiological research2026
Task-Specific Effects of mGlu2/3 Receptor Agonist LY379268 on MK-801-Induced Behavioral and Neural Dysfunctions in Rats.
Article in Physiological research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
NMDA receptor hypofunction can lead to behavioral and cognitive disturbances, including hyperlocomotion, and is considered a core pathophysiological mechanism underlying cognitive and negative symptoms in schizophrenia. This study examined whether treatment with the mGlu2/3 receptor agonist LY379268 (1 and 2 mg/kg) could counteract such disruptions induced by the NMDA antagonist MK-801 (0.1 mg/kg). Rats were tested under two conditions: an aversive learning task (active place avoidance on a rotating arena) and a non-aversive open field test. Additionally, local field potentials were recorded from the medial prefrontal cortex during the open field test and later under urethane anesthesia. Contrary to expectations, LY379268 did not consistently alleviate MK-801-induced impairments. In the aversive learning context, the combination of MK-801 with LY379268 (2 mg/kg) paradoxically led to exacerbated hyperlocomotion and impaired navigational performance. In contrast, the 1 mg/kg dose of LY379268 had a modest beneficial effect in the non-aversive setting, slightly reducing MK-801-induced hyperactivity. Electrophysiological recordings revealed that MK-801, alone or in combination with LY379268 (1 mg/kg), disrupted theta-high gamma phase-amplitude coupling in the open field test, indicating impaired neural processing. Under anesthesia, MK-801 increased low gamma power. LY379268 did not reverse this alteration. These findings highlight the task- and dose-dependent nature of LY379268's effects. While it offered limited improvement in a non-aversive environment, it failed to mitigate and sometimes exacerbated deficits in more challenging, aversive tasks. This complexity underscores the need for further research to refine the therapeutic potential of mGlu2/3 modulation in conditions associated with glutamatergic dysfunction. Key words MK-801 " LY379268 " Electrophysiology " Medial prefrontal cortex " Hyperlocomotion.
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41823094PMC13127986What OpenQuestion holds
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