mGluR5 mediates ketamine antidepressant response in susceptible rats exposed to prenatal stress

Prenatal stress induced depressive‐like behavior and region dependently high CRP level in offspring rats

“…SPT as a well‐recognized evaluation tool of depression and it can effectively detect the presence or absence of anhedonia, which is the core symptom of depression (Overstreet, 2012; Yan et al., 2010). We have previously reported that offspring rats exposed to PS show a graded sucrose‐intake, while no concurrent reduction in water intake (Sun et al., 2017; Wang et al., 2020; Zhang, He, et al., 2019). These changes were also confirmed by many other literatures using chronic mild stress rat model (Bisgaard et al., 2007; Henningsen et al., 2012).…”

“…Inflammation is also known to influence glutamate neurotransmission by binding to its NMDA receptors, leading to chaotic, noisy, incoherent signaling activity in the short‐term, and synaptic toxicity by suppressing intracellular survival mechanisms in the long‐term (Hardingham & Bading, 2010; Haroon et al., 2018). Our previous work has indicated that PS could increase glutamate level in hippocampus (Zhang, He, et al., 2019), decrease NMDA subunit NR1 and NR2 (Sun et al., 2013) and decrease postsynaptic density (PSD)‐95 which was normalized by antidepressant treatment (Wang et al., 2020). Our previous work also manifested that the key receptor of endocannabinoid system CB1 and the key receptor of glucocorticoid system GR were also changed in offspring rats exposed by PS (Sun et al., 2017; Wang et al., 2020; Zhang, He, et al., 2019).…”

“…Our previous work has indicated that PS could increase glutamate level in hippocampus (Zhang, He, et al., 2019), decrease NMDA subunit NR1 and NR2 (Sun et al., 2013) and decrease postsynaptic density (PSD)‐95 which was normalized by antidepressant treatment (Wang et al., 2020). Our previous work also manifested that the key receptor of endocannabinoid system CB1 and the key receptor of glucocorticoid system GR were also changed in offspring rats exposed by PS (Sun et al., 2017; Wang et al., 2020; Zhang, He, et al., 2019). Thus, our present work extended the hypothesis that neuroinflammation, neurotransmitter, and endocrine system were co‐involvement in the pathogenesis of depression.…”

“…In humans, it was reported that prenatal stress could cause neurodevelopment, cognitive development, negative affectivity, and difficult temperament, which are all high risks for subsequent depression in life (Lautarescu et al., 2020; Van den Bergh et al., 2017), even more directly cause depression symptoms in adolescent (Murphy et al., 2017). These depressive symptoms had also been imitated in animal experiments of our and other research teams, which showed depressive‐like behaviors including extended immobile time in forced swimming test (FST), reduced total number of grids explored, number of times, the center grid was crossed, number of times rat stood vertically erect, and time spent in the central grid in open‐field test (OFT), decreased percentage preference for sucrose in sucrose preference test (SPT) (Lu et al., 2020; Wang et al., 2020). Under the mechanism of these clinical phenomena and experimental results, a recent review suggested that neuroinflammation is a key factor that interacts with neurobiological correlates of major depressive disorder and neuroinflammation may be a key therapeutic target for future therapeutic strategies in major depressive disorder (Troubat et al., 2020).…”

Effects of two inhibitors of metabolic glutamate receptor 5 on expression of endogenous homer scaffold protein 1 in the auditory cortex of mice with tinnitus

“…2-Methyl-6-(phenylethynyl)-pyridine (MPEP; formula: C₁₄H₁₁N) is a potent, noncompetitive, orally active, and systemically active mGluR5 antagonist, while α-methyl-4-carboxyphenylglycine (MCPG; formula: C₁₀H₁₁NO₄) is a phenylglycine derivative and a competitive mGluR5 antagonist. Both MPEP and MCPG have been suggested to have antidepressant-like effects in rodents [ 20 , 21 ].…”