Task-Specific Effects of mGlu2/3 Receptor Agonist LY379268 on MK-801-Induced Behavioral and Neural Dysfunctions in Rats.
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...
| Published in: | Physiological Research Vol. 75; no. 1; pp. 149 - 167 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Published: |
Institute of Physiology, Academy of Sciences of the Czech Republic
Feb2026
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=192471954&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 192471954 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 08628408 1CVW jtl: Physiological Research issn: 08628408 maglogo: N pubinfo: dt: Feb2026 vid: 75 iid: 1 pid: 24634 pub: Institute of Physiology, Academy of Sciences of the Czech Republic artinfo: ui: 192471954 10.33549/physiolres.935715 192471954 ppf: 149 ppct: 18 formats: fmt: @attributes: type: P tig: atl: Task-Specific Effects of mGlu2/3 Receptor Agonist LY379268 on MK-801-Induced Behavioral and Neural Dysfunctions in Rats. aug: au: HRUZA, Karolina CERNOTOVA, Daniela MALENINSKA, Kristyna SVOBODA, Jan LEVCIK, David STUCHLIK, Ales affil: Laboratory of the Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic sug: ab: 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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