Increased levels of serotonin2A receptors and serotonin transporter in the CNS of neuregulin 1 hypomorphic/mutant mice

Dean, Brian; Karl, Tim; Pavey, Geoffrey; Boer, Simone; Duffy, Liesl; Scarr, Elizabeth

doi:10.1016/j.schres.2007.10.013

Cited by 38 publications

(22 citation statements)

References 57 publications

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“…Both younger and older mice also showed modest increases in NMDAR binding in sensory, motor and cingulate cortices. These findings contrast with two other studies that used the same Nrg1 model, but found no genotype related differences in NMDAR binding in adult (20-27 weeks) mice (Dean et al 2008;Long et al 2012), although variable levels of environmental enrichment, which has been found to affect NMDAR subunit expression (Guilarte et al 2003), may have been a factor in these studies. Two further studies employing the TM Nrg1 model found reduced NMDAR subunit phosphorylation in both hippocampus (Bjarnadottir et al 2007) and prelimbic (i.e.…”

Section: Nrg1 and Excitatory Neurotransmissioncontrasting

confidence: 99%

Neuregulin-1 and schizophrenia in the genome-wide association study era

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Lloyd

Liberg

et al. 2016

Neuroscience & Biobehavioral Reviews

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Section: Nrg1 and Excitatory Neurotransmissioncontrasting

confidence: 99%

Neuregulin-1 and schizophrenia in the genome-wide association study era

Mostaid

Lloyd

Liberg

et al. 2016

Neuroscience & Biobehavioral Reviews

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“…GABAA-R expression level differences vary between receptor subtypes and brain regions in individuals with schizophrenia (Benes et al, 1996a(Benes et al, , 1996bDuncan et al, 2010). The reduction in NMDA-R and GABAA-R binding supports our two-hit modelling strategy as neither NRG1 HET mice nor chronic PCP treatment alone showed such robust impairments in the present study or in previously published experiments (Beninger et al, 2010;Bullock et al, 2009;Dean et al, 2008;Hanania et al, 1999;Lindahl and Keifer, 2004;Long et al, 2013Long et al, , 2012Newell et al, 2013;Stefansson et al, 2002;Wang et al, 2005). Cognitive and memory functions rely on balanced glutamatergic and GABAergic neurotransmission (Klausberger and Somogyi, 2008).…”

Section: The Two-hit Nrg1-pcp Model Shows Reduced Nmda-r and Gabaa-r supporting

confidence: 86%

mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia

et al. 2016

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Rationale An imbalance of excitatory and inhibitory neurotransmission underlies the glutamate hypothesis of schizophrenia. Agonists of group II metabotropic glutamate receptors, mGluR2/3, have been proposed as novel therapeutic agents to correct this imbalance. However, the influence of mGluR2/3 activity on excitatory and inhibitory neurotransmitter receptors has not been explored. Objectives We aimed to investigate the ability of a novel mGluR2/3 agonist, LY379268, to modulate the availability of the excitatory N-methyl-daspartate receptor (NMDA-R) and the inhibitory gamma-aminobutyrate-A receptor (GABAA-R), in a twohit mouse model of schizophrenia. Methods Wild type (WT) and heterozygous neuregulin 1 transmembrane domain mutant mice (NRG1 HET) were treated daily with phencyclidine (10 mg/kg ip) or saline for 14 days. After a 14-day washout, an acute dose of the mGluR2/3 agonist LY379268 (3 mg/kg), olanzapine (antipsychotic drug comparison, 1.5 mg/kg), or saline was administered. NMDA-R and GABAA-R binding densities were examined by receptor autoradiography in several schizophrenia-relevant brain regions. Results In both WT and NRG1 HET mice, phencyclidine treatment significantly reduced NMDA-R and GABAA-R binding density in the prefrontal cortex, hippocampus, and nucleus accumbens. Acute treatment with LY379268 restored NMDA-R and GABAA-R levels in the two-hit mouse model comparable to olanzapine. Conclusions We demonstrate that the mGluR2/3 agonist LY379268 restores excitatory and inhibitory deficits with similar efficiency as olanzapine in our two-hit schizophrenia mouse model. This study significantly contributes to our understanding of the mechanisms underlying the therapeutic effects of LY379268 and supports the use of agents aimed at mGluR2/3. Disciplines Medicine and Health Sciences Publication DetailsEngel, M., Snikeris, P., Matosin, N., Newell, K. Anne., Huang, X. & Frank, E. (2016). mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia. Psychopharmacology, 233 (8) AcknowledgmentsThis work was supported by the Schizophrenia Research Institute, utilising infrastructure funding from the NSW Ministry of Health. LY379268 was kindly gifted by Eli Lilly & Co (Indianapolis, USA). The funding bodies had no role in the study design, data collection and publication decisions. 2 AbstractRationale An imbalance of excitatory and inhibitory neurotransmission underlies the glutamate hypothesis of schizophrenia. Agonists of Group II metabotropic glutamate receptors, mGluR2/3, have been proposed as novel therapeutic agents to correct this imbalance. However, the influence of mGluR2/3 activity on excitatory and inhibitory neurotransmitter receptors has not been explored.Objectives We aimed to investigate the ability of a novel mGluR2/3 agonist, LY379268, to modulate the availability of the excitatory N-methyl-D-aspartate receptor (NMDA-R) and the inhibitory gamma-aminobutyrate-A receptor (GABAA-R), in a two-hit mouse model of schizophrenia.Me...

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“…2 and 3). These results indicate that non-significant increases in [ 3 H] SCH 23390 binding occurred in the regions assessed in cannabinoid treated rats compared to controls, the sum of these changes resulting in the significant, region-wide effect of HU210 treatment on [ 3 H] SCH 23390 binding (Dean et al, 2008).…”

Section: [ 3 H] Sch 23390 Binding In Adolescent Rats Following a Singmentioning

confidence: 79%

Differential treatment regimen-related effects of cannabinoids on D1 and D2 receptors in adolescent and adult rat brain

Dalton

Zavitsanou

2010

Journal of Chemical Neuroanatomy

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Increased levels of serotonin2A receptors and serotonin transporter in the CNS of neuregulin 1 hypomorphic/mutant mice

Cited by 38 publications

References 57 publications

Neuregulin-1 and schizophrenia in the genome-wide association study era

Neuregulin-1 and schizophrenia in the genome-wide association study era

mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia

Differential treatment regimen-related effects of cannabinoids on D1 and D2 receptors in adolescent and adult rat brain

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