Differential effects of dopamine and serotonin on reward and punishment processes in humans: A systematic review and meta-analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Importance To support treatment assignment, mechanistic biomarkers should be selectively sensitive to specific interventions. Here, we examine whether different components of reinforcement learning in humans satisfy this necessary precondition. We focus on pharmacological manipulations dopamine and serotonin that form the backbone first-line management common mental illnesses such as depression anxiety. Objective perform a meta-analysis they show distinct associations with humans. Data Sources Ovid MEDLINE/PubMed, Embase, PsycInfo databases were searched for studies published between January 1, 1946 19, 2023 (repeated April 9, 2024, October 15, 2024) investigating dopaminergic or serotonergic effects reward/punishment processes humans, according PRISMA guidelines. Study Selection Studies reporting randomized, placebo-controlled, behavioral outcome from processing task healthy included. Extraction Synthesis Standardized mean difference (SMD) scores calculated comparison each drug (dopamine/serotonin) placebo reward punishment quantified random-effects models overall four main subcategories. quality (Cochrane Collaboration’s tool), moderators, heterogeneity, publication bias also assessed. Main Outcome(s) Measure(s) Performance tasks. Results In total, 68 39 volunteers included (N =2291, N =2284; =1491, =1523). Dopamine was associated an increase (SMD=0.18, 95%CI [0.09 0.28]) but not function (SMD=-0.06, [−0.26,0.13]). Serotonin meaningfully (SMD=0.22, [−0.04,0.49]) (SMD=0.02, [−0.33,0.36]). Importantly, had subcomponents. learning/sensitivity (SMD=0.26, [0.11,0.40]), discounting (SMD=-0.08, [−0.14,-0.01]) vigor (SMD=0.32, [0.11,0.54]). By contrast, [0.05,0.59]), (SMD=-0.35, [−0.67,-0.02]), aversive Pavlovian (within-subject only; SMD=0.36, [0.20,0.53]). Conclusions Relevance Pharmacological both have measurable The selective suggests tasks could basis selective, mechanistically interpretable assignment. Key points Question Do affect humans? Findings Upregulating is increased response vigor, decreased discounting. Upregulation Meaning dissociable learning. This forms development markers

Language: Английский

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Assessment of Infant Exposure to Antidepressants through Breastfeeding: A Literature Review of Currently Available Approaches

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(7), P. 847 - 847

Published: June 22, 2024

Despite the prevalence of depression in lactating mothers, there is a lack knowledge about excretion antidepressants into breast milk and its potential adverse effects on infants. This creates concern, making depressed mothers more likely to avoid pharmacological treatment. Clinical lactation studies are most accurate direct method predict demonstrate human milk, results from clinical can be included drug labels help physicians patients make decisions antidepressant use during lactation. However, limited trials pharmacokinetics women because enrollment ethical confounding factors, creating this area. To bridge gap knowledge, alternative methods should sought estimate concentration which used assess safety transfer milk. We provide comprehensive review usage these cost-effective, time-efficient, ethically feasible that serve valuable estimation before conducting studies.

Language: Английский

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Obstructive Sleep Apnea and Serotoninergic Signalling Pathway: Pathomechanism and Therapeutic Potential

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9427 - 9427

Published: Aug. 30, 2024

Obstructive Sleep Apnea (OSA) is a disorder characterized by repeated upper airway collapse during sleep, leading to apneas and/or hypopneas, with associated symptoms like intermittent hypoxia and sleep fragmentation. One of the agents contributing OSA occurrence development seems be serotonin (5-HT). Currently, research focuses on establishing interlinking pathogenesis severity disease molecular neurotransmitter omnipresent in human body—serotonin, its pathway, products, receptors, drugs affecting levels serotonin, or genetic predisposition. The 5-HT system numerous physiological processes such as digestion, circulation, respiration, muscle tone—all which are considered factors promoting influencing course because correlations comorbid conditions. Comorbidities include obesity, behavioral disorders well cardiovascular diseases. Additionally, both imbalance connected psychiatric comorbidities, depression, anxiety, cognitive dysfunction. Pharmacological that target receptors have shown varying degrees efficacy reducing Apnea-Hypopnea Index improving symptoms. potential role signaling pathway modulating provides promising avenue for new therapeutic interventions could accompany primary treatment OSA—continuous positive pressure. Thus, this review aims elucidate complex regulatory mechanisms pathophysiology, evaluating target. We also summarize relationship between various functions,

Language: Английский

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Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knock-Out Mice: A Novel Model for Experience-Based Depression and Post-traumatic Stress Disordertabolism: Insights From Novel Kynurenine Aminotransferase

Published: May 7, 2024

Memory and emotion are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD), which has been linked serotonin (5-HT) metabolism disruptions. In fact, over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via Trp-kynurenine (KYN) meta-bolic pathway, producing a variety bioactive molecules. The aadat (kat2) gene encodes mito-chondrial kynurenine aminotransferase (KAT) isotype 2, responsible for kynurenic acid (KYNA) production. Little known about its role in behavior. CRISPR/Cas9-induced knockout (kat2−/−) mice, we examined effects on emotion, memory, motor function, Trp metabolite levels, enzyme activities plasma urine 8-week-old males compared wild-type mice. Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma levels generally consistent with those urine: KYN, antioxidant KYNs, 5-hydroxyindolacetic acid, indole-3-acetic lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase higher; ox-idative excitotoxicity indices higher. show depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift toward KYN-3-HK partial gut microbial Trp-indole pathway metabolite. This first evidence that deleting causes unique despair experience, appears be excitatory neurotoxic oxidative stresses. may lead development double-hit preclinical model experience-based depression, better understanding these complex condi-tions, effective therapeutic strategies by elucidating relationship between me-tabolism PTSD pathogenesis.

Language: Английский

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Methylphenidate, but not citalopram, decreases impulsive choice in rats performing a temporal discounting task

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: May 8, 2024

Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine can modulate distinct aspects impulsivity - though such tests are often performed using behavioral tasks prohibiting easy comparisons. Here, we directly compare pharmacologic agents affect (methylphenidate) vs (citalopram) manipulations on choice in temporal discounting task where rats could choose between small, immediate reward or large delayed at either 2 10s. In conditions, preferred small (2s) delay discounted long (10s) delay. Methylphenidate, transport inhibitor blocks dopamine, dose-dependently increased preference block. Citalopram, selective inhibitor, had no effect behavior. Impulsive behavior was least partially mediated by nucleus accumbens shell. Bilateral lesions to shell reduced during Following lesions, methylphenidate did not impact impulsivity. Our results suggest striatal dopaminergic via actions within shell, whereas may regulate different inhibition/impulsivity.

Language: Английский

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