Effects of haloperidol, olanzapine, ziprasidone, and <scp>PHA</scp>‐543613 on spatial learning and memory in the Morris water maze test in naïve and <scp>MK</scp>‐801‐treated mice

Ning, Houxu; Dong, Changfeng; Wang, Haidong; Kang, Bing; Xie, Shusen; Meng, Yujing

doi:10.1002/brb3.764

Cited by 30 publications

(10 citation statements)

References 50 publications

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“…Typical antipsychotic drugs not only increase the risk of EPS, but also increase the risk of cognitive impairment (Jeste et al, 1999;Dolder and Jeste, 2003). Many studies have reported impaired memory function after given HAL (Terry et al, 2002;Hou et al, 2006;Abdel-Salam et al, 2012;Ozdemir et al, 2012;Ning et al, 2017), and our results are consistent with these findings. The mechanisms in which HAL induces memory impairment is not clear.…”

Section: Discussionsupporting

confidence: 91%

Dose Effects of Histone Deacetylase Inhibitor Tacedinaline (CI-994) on Antipsychotic Haloperidol-Induced Motor and Memory Side Effects in Aged Mice

2021

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Background: Elderly patients treated with antipsychotic drugs often experience increased severity and frequency of side effects, yet the mechanisms are not well understood. Studies from our group indicate age-related histone modifications at drug targeted receptor gene promoters may contribute to the increased side effects, and histone deacetylase (HDAC) inhibitors entinostat (MS-275) and valproic acid (VPA) could reverse typical antipsychotic haloperidol (HAL) induced motor-side effects. However, whether such effects could be dose dependent and whether HDAC inhibitors could improve memory function in aged mice is unknown.Methods: We co-treated selective class 1 HDAC inhibitor tacedinaline (CI-994) at different doses (10, 20, and 30 mg/kg) with HAL (0.05 mg/kg) in young (3 months) and aged (21 months) mice for 14 consecutive days, then motor and memory behavioral tests were conducted, followed by biochemical measurements.Results: CI-994 at doses of 10 and 20 mg/kg could decrease HAL-induced cataleptic episodes but only 20 mg/kg was sufficient to improve motor coordination in aged mice. Additionally, CI-994 at 10 and 20 mg/kg mitigate HAL-induced memory impairment in aged mice. Biochemical analyses showed increased acetylation of histone marks H3K27ac and H3K18ac at the dopamine 2 receptor (D2R) gene (Drd2) promoter and increased expression of the Drd2 mRNA and D2R protein in the striatum of aged mice after administration of CI-994 at 20 mg/kg.Conclusions: Our results suggest CI-994 can reduce HAL-induced motor and memory side effects in aged mice. These effects may act through an increase of acetylation at the Drd2 promoter, thereby restoring D2R expression and improving antipsychotic drug action.

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Section: Discussionsupporting

confidence: 91%

Dose Effects of Histone Deacetylase Inhibitor Tacedinaline (CI-994) on Antipsychotic Haloperidol-Induced Motor and Memory Side Effects in Aged Mice

2021

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“…To address possible effects of antipsychotics administered to patients, we determined biodistribution in mice treated for 5 d with cohorts of placebo vs risperidone, aripiprazole, or olanzapine, the 3 most common drugs in the present patient population, at doses equivalent to doses used in humans ( Reagan-Shaw et al, 2008 ; Dawe et al, 2010 ; McOmish et al, 2012 ; Ning et al, 2017 ). Mice were i.v.…”

Section: Methodsmentioning

confidence: 99%

Brain PET Imaging of α7-nAChR with [18F]ASEM: Reproducibility, Occupancy, Receptor Density, and Changes in Schizophrenia

Wong

Kuwabara

Horti

et al. 2018

International Journal of Neuropsychopharmacology

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BackgroundThe α7 nicotinic acetylcholine receptor increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7 nicotinic acetylcholine receptor suggests a role in cognition.MethodsWe expanded the first-in-human PET imaging of α7 nicotinic acetylcholine receptor with [18F]ASEM from 5 to 21 healthy nonsmoking volunteers and added a feasibility study in 6 male patients with schizophrenia. Study aims included: (1) confirmation of test-retest reproducibility of [18F]ASEM binding, (2) demonstration of specificity by competition with DMXB-A, an α7 nicotinic acetylcholine receptor partial agonist, (3) estimation of [18F]ASEM binding potentials and α7 nicotinic acetylcholine receptor density in vivo in humans, and (4) demonstrating the feasibility of studying α7 nicotinic acetylcholine receptor as a target for schizophrenia.ResultsTest-retest PET confirmed reproducibility (>90%) (variability ≤7%) of [18F]ASEM volume of distribution (VT) estimates in healthy volunteers. Repeated sessions of PET in 5 healthy subjects included baseline and effect of inhibition after oral administration of 150 mg DMXB-A. From reduction of binding potentials, we estimated the dose-dependent occupancy of α7 nicotinic acetylcholine receptor by DMXB-A at 17% to 49% for plasma concentrations at 60 to 200 nM DMXB-A. In agreement with evidence postmortem, α7 nicotinic acetylcholine receptor density averaged 0.67 to 0.82 nM and inhibitor affinity constant averaged 170 to 385 nM. Median VT in a feasibility study of 6 patients with schizophrenia was lower than in healthy volunteers in cingulate cortex, frontal cortex, and hippocampus (P = 0.02, corrected for multiple comparions, Mann–Whitney test).ConclusionsThe current results confirm the reproducibility of [18F]ASEM VT estimates and the specificity of the tracer for α7 nicotinic acetylcholine receptor. Preliminary findings from our feasibility study of [18F]ASEM binding in patients with schizophrenia are suggestive and provide guidance for future studies with more subjects.

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“…The MWM test is a classic method for detecting spatial learning and memory abilities 32 , 33 . Long-term exposure to 2.856 GHz microwaves prolonged the AELs in rats in a previous study 5 , but this study examined only the effects of one microwave frequency.…”

Section: Discussionmentioning

confidence: 99%

Acute effects of 2.856 GHz and 1.5 GHz microwaves on spatial memory abilities and CREB-related pathways

Tan¹,

Wang²,

Xu³

et al. 2021

Sci Rep

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This study aimed to evaluate the acute effects of 2.856 GHz and 1.5 GHz microwaves on spatial memory and cAMP response element binding (CREB)-related pathways. A total of 120 male Wistar rats were divided into four groups: a control group (C); 2.856 GHz microwave exposure group (S group); 1.5 GHz microwave exposure group (L group); and 2.856 and 1.5 GHz cumulative exposure group (SL group). Decreases in spatial memory abilities, changes in EEG, structural injuries, and the downregulation of phosphorylated-Ak strain transforming (p-AKT), phosphorylated-calcium/calmodulin-dependent protein kinase II (p-CaMKII), phosphorylated extracellular signal regulated kinase (p-ERK) and p-CREB was observed 6 h after microwave exposure. Significant differences in the expression of p-CaMKII were found between the S and L groups. The power amplitudes of the EEG waves (θ, δ), levels of structural injuries and the expression of p-AKT, p-CaMK II, p-CREB, and p-ERK1/2 were significantly different in the S and L groups compared to the SL group. Interaction effects between the 2.856 and 1.5 GHz microwaves were found in the EEG and p-CREB changes. Our findings indicated that 2.856 GHz and 1.5 GHz microwave exposure induced a decline in spatial memory, which might be related to p-AKT, p-CaMK II, p-CREB and p-ERK1/2.

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Effects of haloperidol, olanzapine, ziprasidone, and PHA‐543613 on spatial learning and memory in the Morris water maze test in naïve and MK‐801‐treated mice

Cited by 30 publications

References 50 publications

Dose Effects of Histone Deacetylase Inhibitor Tacedinaline (CI-994) on Antipsychotic Haloperidol-Induced Motor and Memory Side Effects in Aged Mice

Dose Effects of Histone Deacetylase Inhibitor Tacedinaline (CI-994) on Antipsychotic Haloperidol-Induced Motor and Memory Side Effects in Aged Mice

Brain PET Imaging of α7-nAChR with [18F]ASEM: Reproducibility, Occupancy, Receptor Density, and Changes in Schizophrenia

Acute effects of 2.856 GHz and 1.5 GHz microwaves on spatial memory abilities and CREB-related pathways

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