Schizophrenia-like olfactory dysfunction induced by acute and postnatal phencyclidine exposure in rats

Shan, Liang; Liu, Tiane; Zhang, Zhijian; Liu, Qing; Zhang, Mengjiao; Zhao, Xudong; Zhang, Yan; Xu, Fuqiang; Ma, Yuanye

doi:10.1016/j.schres.2018.02.045

Cited by 4 publications

(1 citation statement)

References 29 publications

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“…Indeed, published works that have commonly reported the application of lower doses of PCP (2–5 mg/kg) are those conducted in rats (Bruins Slot et al, 2005; Dawson et al, 2012; Egerton et al, 2008; Lee et al, 2005; Snigdha and Neill, 2008), whereas in mice higher doses, typically around 10 mg/kg once per day, as applied here, have most commonly been used (Fujita et al, 2008; Hashimoto et al, 2007; 2008; Santini et al, 2013; Tanibuchi et al, 2009). There are also a limited number of subchronic PCP studies that have utilised a 10 mg/kg dosing regimen in adult rats (Audet et al, 2009; Martinez et al, 1999) and this dose has been applied in developmental rat models employing early postnatal administration (Andrews et al, 2018; Shan et al, 2018), albeit with less frequency. Our own experience with using PCP in both species indicates that mice are somewhat less sensitive to the acute effects of PCP than rats, although the field is currently lacking a systematic comparison between the two species, which would be of great benefit.…”

Section: Discussionmentioning

confidence: 99%

Sustained NMDA receptor hypofunction impairs brain-derived neurotropic factor signalling in the PFC, but not in the hippocampus, and disturbs PFC-dependent cognition in mice

et al. 2021

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Background: Cognitive deficits profoundly impact on the quality of life of patients with schizophrenia. Alterations in brain derived neurotrophic factor (BDNF) signalling, which regulates synaptic function through the activation of full-length tropomyosin-related kinase B receptors (TrkB-FL), are implicated in the aetiology of schizophrenia, as is N-methyl-D-aspartate receptor (NMDA-R) hypofunction. However, whether NMDA-R hypofunction contributes to the disrupted BDNF signalling seen in patients remains unknown. Aims: The purpose of this study was to characterise BDNF signalling and function in a preclinical rodent model relevant to schizophrenia induced by prolonged NMDA-R hypofunction. Methods: Using the subchronic phencyclidine (PCP) model, we performed electrophysiology approaches, molecular characterisation and behavioural analysis. Results: The data showed that prolonged NMDA-R antagonism, induced by subchronic PCP treatment, impairs long-term potentiation (LTP) and the facilitatory effect of BDNF upon LTP in the medial prefrontal cortex (PFC) of adult mice. Additionally, TrkB-FL receptor expression is decreased in the PFC of these animals. By contrast, these changes were not present in the hippocampus of PCP-treated mice. Moreover, BDNF levels were not altered in the hippocampus or PFC of PCP-treated mice. Interestingly, these observations are paralleled by impaired performance in PFC-dependent cognitive tests in mice treated with PCP. Conclusions: Overall, these data suggest that NMDA-R hypofunction induces dysfunctional BDNF signalling in the PFC, but not in the hippocampus, which may contribute to the PFC-dependent cognitive deficits seen in the subchronic PCP model. Additionally, these data suggest that targeting BDNF signalling may be a mechanism to improve PFC-dependent cognitive dysfunction in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Sustained NMDA receptor hypofunction impairs brain-derived neurotropic factor signalling in the PFC, but not in the hippocampus, and disturbs PFC-dependent cognition in mice

et al. 2021

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Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species

Cothren

Evonko

MacQueen

2022

Current Topics in Behavioral Neurosciences

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Advances in the study of phencyclidine-induced schizophrenia-like animal models and the underlying neural mechanisms

Li,

Pan,

Xiao

et al. 2024

Schizophr

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Schizophrenia (SZ) is a chronic, severe mental disorder with heterogeneous clinical manifestations and unknown etiology. Research on SZ has long been limited by the low reliability of and ambiguous pathogenesis in schizophrenia animal models. Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, rapidly induces both positive and negative symptoms of SZ as well as stable SZ-related cognitive impairment in rodents. However, the neural mechanism underlying PCP-induced SZ-like symptoms is not fully understood. Nondopaminergic pathophysiology, particularly excessive glutamate release induced by NMDAR hypofunction in the prefrontal cortex (PFC), may play a key role in the development of PCP-induced SZ-like symptoms. In this review, we summarize studies on the behavioral and metabolic effects of PCP and the cellular and circuitary targets of PCP in the PFC and hippocampus (HIP). PCP is thought to target the ventral HIP-PFC pathway more strongly than the PFC-VTA pathway and thalamocortical pathway. Systemic PCP administration might preferentially inhibit gamma-aminobutyric acid (GABA) neurons in the vHIP and in turn lead to hippocampal pyramidal cell disinhibition. Excitatory inputs from the HIP may trigger sustained, excessive and pathological PFC pyramidal neuron activation to mediate various SZ-like symptoms. In addition, astrocyte and microglial activation and oxidative stress in the cerebral cortex or hippocampus have been observed in PCP-induced models of SZ. These findings perfect the hypoglutamatergic hypothesis of schizophrenia. However, whether these effects direct the consequences of PCP administration and how about the relationships between these changes induced by PCP remain further elucidation through rigorous, causal and direct experimental evidence.

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Schizophrenia-like olfactory dysfunction induced by acute and postnatal phencyclidine exposure in rats

Cited by 4 publications

References 29 publications

Sustained NMDA receptor hypofunction impairs brain-derived neurotropic factor signalling in the PFC, but not in the hippocampus, and disturbs PFC-dependent cognition in mice

Sustained NMDA receptor hypofunction impairs brain-derived neurotropic factor signalling in the PFC, but not in the hippocampus, and disturbs PFC-dependent cognition in mice

Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species

Advances in the study of phencyclidine-induced schizophrenia-like animal models and the underlying neural mechanisms

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