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  2. The metabotropic glutamate receptor 2/3 antagonist LY341495 improves working memory in adult mice following juvenile social isolation

The metabotropic glutamate receptor 2/3 antagonist LY341495 improves working memory in adult mice following juvenile social isolation

  • Neuropharmacology. 2020 Oct 15;177:108231. doi: 10.1016/j.neuropharm.2020.108231.
Xiao-Qin Zhang 1 He-Jia Jiang 2 Le Xu 2 Si-Yu Yang 2 Gao-Zhe Wang 2 Hong-De Jiang 2 Teng Wu 2 Han Du 2 Zhi-Peng Yu 2 Qi-Qi Zhao 2 Yu Ling 2 Zhong-Yu Zhang 3 Hao-Wei Shen 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, Ningbo University School of Medicine, 818 Fenghua Rd, Ningbo, Zhejiang, 315211, China; Key Laboratory of Addiction Research of Zhejiang Province, Ningbo 315010, PR China.
  • 2 Department of Pharmacology, Ningbo University School of Medicine, 818 Fenghua Rd, Ningbo, Zhejiang, 315211, China.
  • 3 Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Beijing, 100191, China.
  • 4 Department of Pharmacology, Ningbo University School of Medicine, 818 Fenghua Rd, Ningbo, Zhejiang, 315211, China; Key Laboratory of Addiction Research of Zhejiang Province, Ningbo 315010, PR China. Electronic address: shenhaowei@nbu.edu.cn.
Abstract

Juvenile social isolation (SI) and neglect have a negative impact on neurodevelopment persistently, which is associated with cognitive dysfunction in neurodevelopmental disorders. Given the critical role of Metabotropic Glutamate Receptors (mGluRs) in synaptic homeostasis of the prefrontal cortex (PFC), pharmacological intervention on mGluRs has been attempted in order to improve cognitive dysfunction in animal models of neurodevelopmental disorder, as well as in clinical trials. Here we examined the effects of the mGluR2/3 antagonist LY341495 on prefrontal synaptic transmission, spatial working memory, and recognition memory in adult C57BL/6J mice that experienced juvenile SI. We found that SI-reared mice exhibited working memory impairment and decreased excitatory presynaptic release probability of pyramidal neurons in the medial PFC compared with group-reared mice. The positive effect of LY341495 on excitatory synaptic transmission in SI-reared mice was more prominent than the effect in group-reared mice. A single treatment with mGluR2/3 antagonist LY341495 significantly improved the performance of SI-reared mice in the Y-maze test but not in the novel object recognition (NOR) test, while repeated treatments were effective in both tasks. These findings suggest that enhancing glutamatergic transmission via inhibition of mGluR2/3 signaling might represent a promising strategy for improving cognitive function in neurodevelopmental disorders.

Keywords

Cognitive deficits; Excitatory synaptic transmission; Metabotropic glutamate receptors; Social isolation.

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