Molecular profile of ketamine in comparison to memantine and phencyclidyne and other psychotropic drugs
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PROVIDER: PRJNA297898 | ENA |
REPOSITORIES: ENA
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Project description:Ketamine has been found to elicit a rapid antidepressant effects in treatment-refractory affective disorders. To indicate the underlying mechanism of action we have performed whole-genome microarray profiling. Moreover, the effects of ketamine were compared to other NMDA receptor antagonists phencyclidine and memantine. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Ketamine, NMDA antagonist, Phencyclidyne, Memantine, Time-course, Gene Expression, Acute treatment
2015-12-31 | GSE73799 | GEO
Project description:Ketamine has been found to elicit a rapid antidepressant effects in treatment-refractory affective disorders. To indicate the underlying mechanism of action we have performed whole-genome microarray profiling. Moreover, the effects of ketamine were compared to other NMDA receptor antagonists phencyclidine and memantine. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Ketamine, NMDA antagonist, Phencyclidyne, Memantine, Time-course, Gene Expression, Acute treatment
2015-12-31 | GSE73798 | GEO
Project description:Ketamine has been found to elicit a rapid antidepressant effects in treatment-refractory affective disorders. To indicate the underlying mechanism of action we have performed whole-genome microarray profiling. Moreover, the effects of ketamine were compared to other NMDA receptor antagonists phencyclidine and memantine. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Ketamine, NMDA antagonist, Phencyclidyne, Memantine, Time-course, Gene Expression, Acute treatment The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse hippocampus. Three NMDA antagonists (ketamine 20 mg/kg, phencyclidine 5 mg/kg and memantine 15 mg/kg i.p.) were selected for the comparison. Drug doses were based on the literature. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naive animals were prepared for each time point. Samples from 2 mice were pooled per microarray, 3 biological replicates were used per time point and 12 arrays per each drug. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.
2015-12-31 | E-GEOD-73798 | biostudies-arrayexpress
Project description:Ketamine has been found to elicit a rapid antidepressant effects in treatment-refractory affective disorders. To indicate the underlying mechanism of action we have performed whole-genome microarray profiling. Moreover, the effects of ketamine were compared to other NMDA receptor antagonists phencyclidine and memantine. Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays Keywords: Ketamine, NMDA antagonist, Phencyclidyne, Memantine, Time-course, Gene Expression, Acute treatment The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Three NMDA antagonists (ketamine 20 mg/kg, phencyclidine 5 mg/kg and memantine 15 mg/kg i.p.) were selected for the comparison. Drug doses were based on the literature. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naive animals were prepared for each time point. Samples from 2 mice were pooled per microarray, 3 biological replicates were used per time point and 12 arrays per each drug. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches. 'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.
2015-12-31 | E-GEOD-73799 | biostudies-arrayexpress
Project description:Molecular profile of ketamine in comparison to memantine and phencyclidyne and other psychotropic drugs [mouse striatum]
| PRJNA297901 | ENA
Project description:Molecular profile of ketamine in comparison to memantine and phencyclidyne and other psychotropic drugs [mouse hippocampus]
| PRJNA297902 | ENA
Project description:Patients with schizophrenia show increased striatal dopamine synthesis capacity in imaging studies. However, the mechanism underlying this is unclear but may be due to N-methyl-D-aspartate receptor (NMDAR) hypofunction and parvalbumin (PV) neuronal dysfunction leading to disinhibition of mesostriatal dopamine neurons. Here, we test this in a translational mouse imaging study using a ketamine model. Mice were treated with sub-chronic ketamine (30mg/kg) or saline followed by in-vivo positron emission tomography of striatal dopamine synthesis capacity, analogous to measures used in patients. Locomotor activity was measured using the open field test. In-vivo cell-type-specific chemogenetic approaches and pharmacological interventions were used to manipulate neuronal excitability. Immunohistochemistry and RNA sequencing were used to investigate molecular mechanisms. Sub-chronic ketamine increased striatal dopamine synthesis capacity (Cohen’s d=2.5) and locomotor activity. These effects were countered by inhibition of midbrain dopamine neurons, and by activation of cortical and ventral subiculum PV interneurons. Sub-chronic ketamine reduced PV expression in these neurons. Pharmacological intervention with SEP-363856, a novel psychotropic agent with agonism at trace amine receptor 1 (TAAR1), significantly reduced the ketamine-induced increase in dopamine synthesis capacity. These results show that sub-chronic ketamine treatment in mice mimics the dopaminergic alterations in patients with psychosis, and suggest an underlying neurocircuit involving PV interneuron hypofunction in frontal cortex and hippocampus as well as activation of midbrain dopamine neurons. A novel TAAR1 agonist reversed the dopaminergic alterations suggesting a therapeutic mechanism for targeting presynaptic dopamine dysfunction in patients.
2021-02-16 | GSE138802 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-12-31 | GSE73800 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-12-31 | E-GEOD-73800 | biostudies-arrayexpress
Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine.
2016-07-27 | GSE81672 | GEO