Stimulation of the metabotropic glutamate 2/3 receptor attenuates social novelty discrimination deficits induced by neonatal phencyclidine treatment

Harich, Silke; Groß, Gerhard; Bespalov, Anton

doi:10.1007/s00213-007-0742-y

Cited by 99 publications

(72 citation statements)

References 43 publications

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“…Therefore, the improvements induced by LY379268, BINA, and JNJ16259685 on social memory impairment are unlikely to reflect nonspecific effects. Although we used a different animal model, the improvement of social memory impairment by the stimulation of mGlu2/3 receptors is consistent with previous findings that rats treated neonatally with phencyclidine (PCP) exhibited deficits in social discrimination and that an mGlu2/3-receptor agonist improved the deficits in social discrimination (20).…”

Section: Discussionsupporting

confidence: 88%

Stimulation of Metabotropic Glutamate (mGlu) 2 Receptor and Blockade of mGlu1 Receptor Improve Social Memory Impairment Elicited by MK-801 in Rats

et al. 2013

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Abstract. Glutamatergic dysfunction has been implicated in psychiatric disorders such as schizophrenia. Both the stimulation of the metabotropic glutamate (mGlu) 2/3 receptor and the blockade of the mGlu1 receptor have been shown to be effective in a number of animal models of schizophrenia. However, the efficacy for social cognition, which is poorly managed by current medication, has not been fully addressed. The present study evaluated the effects of an mGlu2/3-receptor agonist and an mGlu1-receptor antagonist on social memory impairment in rats. Pretreatment with an mGlu2/3-receptor agonist, (−)-2-oxa-4-aminobicyclo[3. propanoic acid (LY341495). These findings indicate that both the stimulation of the mGlu2 receptor and the inhibition of an mGlu1 receptor improve social memory impairment elicited by MK-801, and both manipulations could be effective approaches for the treatment of certain cognitive dysfunctions observed in schizophrenic patients.

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Section: Discussionsupporting

confidence: 88%

Stimulation of Metabotropic Glutamate (mGlu) 2 Receptor and Blockade of mGlu1 Receptor Improve Social Memory Impairment Elicited by MK-801 in Rats

et al. 2013

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“…Considering current 11 literature and the role that these three proteins play in apoptotic processes, our results suggest that these proteins may have implications in acute PCP induced neurotoxicity and thus may contribute to deficits in brain development, neuronal cytoarchitecture and plasticity of the brain early in the development of schizophrenia.…”

Section: Discussionmentioning

confidence: 78%

“…Due to its effects on a multitude of important receptor targets known to be implicated in the schizophrenia pathology, PCP treatment in rodents has been used to model the glutamate hypofunction hypotheses and dopamine hyperfunction hypotheses of schizophrenia 2,8 . The use of PCP administration at postnatal days (PN)7, 9 and 11 has consistently been shown to induce hyperlocomotion, reduced prepulse inhibition and impaired social interactions in rodents [9][10][11] . The behaviors it induces in rodents in addition to the psychomimetic effects it has in humans, makes it a valid model for studying the development of schizophrenia 12 .…”

Section: Introductionmentioning

confidence: 99%

Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats

Andrews

Newell

Matosin

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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(2015). Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 63 91-97.Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats AbstractPostnatal administration of phencyclidine (PCP) in rodents causes major disturbances to neurological processes resulting in severe modifications to normal behavioral traits into adulthood. It is routinely used to model psychiatric disorders such as schizophrenia, producing many of the dysfunctional processes in the brain that are present in this devastating disorder, including elevated levels of apoptosis during neurodevelopment and disruptions to myelin and plasticity processes. Lingo-1 (or Leucine-rich repeat and immunoglobulin domain-containing protein) is responsible for negatively regulating neurite outgrowth and the myelination of axons. Recent findings using a postmortem human brain cohort showed that Lingo-1 signaling partners in the Nogo receptor (NgR)/p75/TNF receptor orphan Y (TROY) signaling complex, and downstream signaling partners With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1), play a significant part in schizophrenia pathophysiology. Here we have examined the implication of Lingo-1 and its signaling partners in a neurodevelopmental model of schizophrenia using PCP to determine if these pathways are altered in the hippocampus throughout different stages of neurodevelopment. Male Sprague-Dawley rats were injected subcutaneously with PCP (10 mg/kg) or saline solution on postnatal days (PN) 7, 9, and 11. Rats (n = 6/group) were sacrificed at PN12, 5 weeks, or 14 weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001 ≤ p ≤ 0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5 weeks (p > 0.05). At 14 weeks, p75, TROY, and Myt1 were increased in the PCP treated rats (0.014 ≤ p ≤ 0.022). This is the first report of an alteration in Lingo-1 signaling proteins in the rat hippocampus, both directly after PCP treatment in early development and in adulthood. Based on our results, we propose that components of the Lingo-1 signaling pathways may be involved in the acute neurotoxicity induced by perinatal administration of PCP in rats early in development and suggest that this may have implications for the hippocampal deficits seen in schizophrenia. Male Sprague Dawley rats were injected subcutaneously with PCP (10mg/kg) or saline solution on postnatal days (PN)7, 9 and 11. Rats (n=6/group) were sacrificed at PN12, 5 weeks or 14 weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001≤p≤0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5 we...

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“…Impairments in social interaction have also been reported in rats treated with PCP (10 mg/kg, s.c.) on postnatal days 7, 9, and 11 (Harich et al, 2007) and in adolescent rats injected with PCP (9 mg/kg), twice per day at a 12-h interval for two consecutive days. Drug effects were tested during the acute drug state (PD 50-51) and post-drug phase and in adulthood (after PD 80) and PCP was shown to decrease social interaction during the first 8 min of the test (White et al, 2009).…”

mentioning

confidence: 99%

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

477

322

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Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro-and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive disturbances of relevance to schizophrenia in rodents and their subsequent reversal by first-and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-choice serial reaction time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel therapies for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

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Stimulation of the metabotropic glutamate 2/3 receptor attenuates social novelty discrimination deficits induced by neonatal phencyclidine treatment

Abstract: These results suggest that targeting glutamatergic functions may reverse long-term developmental cognitive deficits produced by PCP.

Cited by 99 publications

References 43 publications

Stimulation of Metabotropic Glutamate (mGlu) 2 Receptor and Blockade of mGlu1 Receptor Improve Social Memory Impairment Elicited by MK-801 in Rats

Stimulation of Metabotropic Glutamate (mGlu) 2 Receptor and Blockade of mGlu1 Receptor Improve Social Memory Impairment Elicited by MK-801 in Rats

Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

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