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Muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis: protocol for a systematic review and meta-analysis.
F1000Res
January 2025
German Center for Mental Health (DZPG), partner site München/Augsburg, Munich, Germany.
Background: Muscarinic receptor agonism and positive allosteric modulation is a promising mechanism of action for treating psychosis, not present in most D2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists and positive allosteric modulators in animal models of psychosis to provide unique insights and evidence-based information to guide drug development.
View Article and Find Full Text PDFDistinct Effects of Olanzapine Depot Treatment on Behavior and Muscarinic M1 Receptor Expression in the Triple-Hit Wisket Rat Model of Schizophrenia.
Genes Brain Behav
February 2025
Department of Physiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
This study aimed to characterize the triple-hit schizophrenia-like model rats (Wisket) by the assessment of (1) behavioral parameters in different test conditions (reward-based Ambitus test and HomeManner system) for a prolonged period, (2) cerebral muscarinic M1 receptor (M1R) expression, and (3) the effects of olanzapine treatment on these parameters. Wistar (control) and Wisket rats were injected for three consecutive weeks with olanzapine depot (100 mg/kg) and spent 4 weeks in large cages with environmental enrichment (HomeManner). The vehicle-treated Wisket rats spent longer time awake with decreased grooming activity compared to controls, without changes in their active social behavior (sniffing, playing, fighting) obtained in HomeManner.
View Article and Find Full Text PDFEffect of combination therapy of methylfolate with antidepressants in patients with depressive disorder.
BMC Pharmacol Toxicol
January 2025
Department of Community Medicine, Islamic International Medical College (IIMC), Riphah International University, Rawalpindi, Pakistan.
Objective: To determine the relative effectiveness of combination therapy of antidepressants with low-dose methylfolate versus antidepressant monotherapy in patients with depressive disorder.
Methods: In an open-label clinical trial, forty-four patients with depressive disorder (6A70, 6A71, and 6A72 according to ICD-11) received an evidence-based antidepressant therapy (either escitalopram 10-20 mg, sertraline 50-100 mg, fluoxetine 20-40 mg, duloxetine 30-60 mg, mirtazapine 15-30 mg, venlafaxine 75-150 mg, trazodone 50-100 mg, amitriptyline 25-75 mg, or clomipramine 25-75 mg orally daily for 4 weeks). The experimental group, Group B was additionally given a dose of methylfolate 800 µg daily for four weeks.
The risks of adverse events with mirtazapine for adults with major depressive disorder: a systematic review with meta-analysis and trial sequential analysis.
BMC Psychiatry
January 2025
Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, Copenhagen Ø, DK-2100, Denmark.
Background: Mirtazapine is used to treat depression worldwide, and the effects of mirtazapine on depression rating scales are well-known. Our primary objective was to assess the risks of adverse events with mirtazapine for major depressive disorder.
Methods: We searched relevant sources from inception to 7 March 2024 for randomised clinical trials comparing mirtazapine versus placebo in adults with major depressive disorder.
Rescue-like behavior in a bystander mouse toward anesthetized conspecifics promotes arousal via a tongue-brain connection.
Sci Adv
January 2025
Department of Pain Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Prosocial behaviors are advantageous to social species, but the neural mechanism(s) through which others receive benefit remain unknown. Here, we found that bystander mice display rescue-like behavior (tongue dragging) toward anesthetized cagemates and found that this tongue dragging promotes arousal from anesthesia through a direct tongue-brain circuit. We found that a direct circuit from the tongue → glutamatergic neurons in the mesencephalic trigeminal nucleus (MTN) → noradrenergic neurons in the locus coeruleus (LC) drives rapid arousal in the anesthetized mice that receive the rescue-like behavior from bystanders.
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