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Cancer Science Jul 2023Retraction: Kim, Areumnuri; Lee, Hyunjung; Shim, Sehwan; Kong, Jun Suk; Kim, Min-Jung; Park, Sunhoo; Lee, Seung-Sook, Overexpression of dopamine receptor D2 promotes...
Retraction: Kim, Areumnuri; Lee, Hyunjung; Shim, Sehwan; Kong, Jun Suk; Kim, Min-Jung; Park, Sunhoo; Lee, Seung-Sook, Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β-catenin/ZEB1 axis, Cancer Science 2021, 112 (9), pp. 3732-3743 (https://onlinelibrary.wiley.com/doi/10.1111/cas.15026). The above article, published online on 12 June 2021 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the journal Editor in Chief Masanori Hatakeyama, Japanese Cancer Association and John Wiley and Sons Australia, Ltd. following an investigation based on concerns on figures 1, 2, 3 and 6 raised by the publisher's image integrity team. The corresponding author asked to retract this manuscript as the experimental data in the article could not be reproduced and original data are no longer available to validate the conclusions. The co-authors were not available to confirm the retraction.
PubMed: 37166008
DOI: 10.1111/cas.15838 -
Nature Sep 2023Striatal dopamine and acetylcholine are essential for the selection and reinforcement of motor actions and decision-making. In vitro studies have revealed an...
Striatal dopamine and acetylcholine are essential for the selection and reinforcement of motor actions and decision-making. In vitro studies have revealed an intrastriatal circuit in which acetylcholine, released by cholinergic interneurons (CINs), drives the release of dopamine, and dopamine, in turn, inhibits the activity of CINs through dopamine D2 receptors (D2Rs). Whether and how this circuit contributes to striatal function in vivo is largely unknown. Here, to define the role of this circuit in a living system, we monitored acetylcholine and dopamine signals in the ventrolateral striatum of mice performing a reward-based decision-making task. We establish that dopamine and acetylcholine exhibit multiphasic and anticorrelated transients that are modulated by decision history and reward outcome. Dopamine dynamics and reward encoding do not require the release of acetylcholine by CINs. However, dopamine inhibits acetylcholine transients in a D2R-dependent manner, and loss of this regulation impairs decision-making. To determine how other striatal inputs shape acetylcholine signals, we assessed the contribution of cortical and thalamic projections, and found that glutamate release from both sources is required for acetylcholine release. Altogether, we uncover a dynamic relationship between dopamine and acetylcholine during decision-making, and reveal multiple modes of CIN regulation. These findings deepen our understanding of the neurochemical basis of decision-making and behaviour.
Topics: Animals; Mice; Acetylcholine; Corpus Striatum; Dopamine; Glutamic Acid; Neostriatum; Decision Making; Reward; Receptors, Dopamine D2; Cholinergic Neurons; Neural Pathways
PubMed: 37557915
DOI: 10.1038/s41586-023-06492-9 -
Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y