Evidence for a competitive relationship between executive functions and statistical learning.

The ability of the brain to extract patterns from the environment and predict future events, known as statistical learning, has been proposed to interact in a competitive manner with prefrontal lobe-related networks and their characteristic cognitive or executive functions. However, it remains unclear whether these cognitive functions also possess a competitive relationship with implicit statistical learning across individuals and at the level of latent executive function components. In order to address this currently unknown aspect, we investigated, in two independent experiments (NStudy1 = 186, NStudy2 = 157), the relationship between implicit statistical learning, measured by the Alternating Serial Reaction Time task, and executive functions, measured by multiple neuropsychological tests. In both studies, a modest, but consistent negative correlation between implicit statistical learning and most executive function measures was observed. Factor analysis further revealed that a factor representing verbal fluency and complex working memory seemed to drive these negative correlations. Thus, the antagonistic relationship between implicit statistical learning and executive functions might specifically be mediated by the updating component of executive functions or/and long-term memory access.

The Lectin Pathway of the Complement System-Activation, Regulation, Disease Connections and Interplay with Other (Proteolytic) Systems.

The complement system is the other major proteolytic cascade in the blood of vertebrates besides the coagulation-fibrinolytic system. Among the three main activation routes of complement, the lectin pathway (LP) has been discovered the latest, and it is still the subject of intense research. Mannose-binding lectin (MBL), other collectins, and ficolins are collectively termed as the pattern recognition molecules (PRMs) of the LP, and they are responsible for targeting LP activation to molecular patterns, e.g., on bacteria. MBL-associated serine proteases (MASPs) are the effectors, while MBL-associated proteins (MAps) have regulatory functions. Two serine protease components, MASP-1 and MASP-2, trigger the LP activation, while the third component, MASP-3, is involved in the function of the alternative pathway (AP) of complement. Besides their functions within the complement system, certain LP components have secondary ("moonlighting") functions, e.g., in embryonic development. They also contribute to blood coagulation, and some might have tumor suppressing roles. Uncontrolled complement activation can contribute to the progression of many diseases (e.g., stroke, kidney diseases, thrombotic complications, and COVID-19). In most cases, the lectin pathway has also been implicated. In this review, we summarize the history of the lectin pathway, introduce their components, describe its activation and regulation, its roles within the complement cascade, its connections to blood coagulation, and its direct cellular effects. Special emphasis is placed on disease connections and the non-canonical functions of LP components.

Specifying the timescale of early life unpredictability helps explain the development of internalising and externalising behaviours.

Early life unpredictability is associated with both physical and mental health outcomes throughout the life course. Here, we classified adverse experiences based on the timescale on which they are likely to introduce variability in children's environments: variations unfolding over short time scales (e.g., hours, days, weeks) and labelled Stochasticity vs variations unfolding over longer time scales (e.g., months, years) and labelled Volatility and explored how they contribute to the development of problem behaviours. Results indicate that externalising behaviours at age 9 and 15 and internalising behaviours at age 15 were better accounted for by models that separated Stochasticity and Volatility measured at ages 3 to 5. Both externalising and internalising behaviours were specifically associated with Volatility, with larger effects for externalising behaviours. These findings are interpreted in light of evolutionary-developmental models of psychopathology and reinforcement learning models of learning under uncertainty.

The complexity of measuring reliability in learning tasks: An illustration using the Alternating Serial Reaction Time Task.

Despite the fact that reliability estimation is crucial for robust inference, it is underutilized in neuroscience and cognitive psychology. Appreciating reliability can help researchers increase statistical power, effect sizes, and reproducibility, decrease the impact of measurement error, and inform methodological choices. However, accurately calculating reliability for many experimental learning tasks is challenging. In this study, we highlight a number of these issues, and estimate multiple metrics of internal consistency and split-half reliability of a widely used learning task on a large sample of 180 subjects. We show how pre-processing choices, task length, and sample size can affect reliability and its estimation. Our results show that the Alternating Serial Reaction Time Task has respectable reliability, especially when learning scores are calculated based on reaction times and two-stage averaging. We also show that a task length of 25 blocks can be sufficient to meet the usual thresholds for minimally acceptable reliability. We further illustrate how relying on a single point estimate of reliability can be misleading, and the calculation of multiple metrics, along with their uncertainties, can lead to a more complete characterization of the psychometric properties of tasks.

Early life adversity jointly regulates body-mass index and working memory development.

Previous work has proposed that balancing energy expenditure towards body and brain development in an optimal fashion results in a negative relationship between somatic and neurocognitive growth during development. An important issue, largely overlooked so far, is the extent to which this energetic trade-off is influenced by early life environmental factors. In this study, we estimated the association between neurocognitive (measured by working memory ability) and somatic (measured by body-mass index) developmental trajectories, while taking into account multiple dimensions of early life adversity. Results of our initial growth curve model were consistent with this brain-body trade-off in both girls and boys. In a subsequent model, we showed that early life adversity had positive associations with somatic and negative associations with neurocognitive growth trajectories, although the direct negative coupling between them remained consistent. Finally, a multidimensional adversity model, separating the effects of deprivation, threat and unpredictability, revealed that the dimension of deprivation-reflecting lack of access to resources and cognitive stimulation-contributed the most to both somatic and neurocognitive growth patterns. These results suggest that the way individuals balance energy between these two biological constructs during development is partly linked to environmental influences through phenotypic plasticity.

The neuropsychological profile of work addiction.

The objective of this study was to examine, for the first time, the neuropsychological aspects of work addiction, with a specific emphasis on the cognitive factors identified by theoretical models. While previous research has highlighted self-reported obsessiveness and impulsiveness in work addiction, this study sought to go beyond self-report measures by employing also neuropsychological reaction time tasks to assess executive functions. A total of 101 participants were categorized into two groups based on their Work Addiction Risk Test scores: a high-risk group (HWA; n = 39) and a low-risk group (LWA; n = 62) for work addiction. Executive functions were assessed using Go/No-Go, Digit Span, Counting Span, N-back, and Card Sorting Tasks. The findings revealed that the HWA group had poorer inhibitory control and achieved lower scores on the more complex working memory task involving updating (2-back). However, they exhibited unaltered cognitive flexibility and outperformed the LWA group on the 1-back task associated with maintenance and storage of information and sustained attention. Higher levels of impulsiveness and compulsiveness were observed in the HWA group, consistent with previous studies. These findings highlight the role of inhibition and working memory in work addiction, potentially contributing to challenges such as inefficient working strategies and impaired social functioning. This study offers valuable insights into the neurocognitive aspects of work addiction, deepening our understanding of this phenomenon.

Quantification of the zymogenicity and the substrate-induced activity enhancement of complement factor D.

Complement factor D (FD) is a serine protease present predominantly in the active form in circulation. It is synthesized as a zymogen (pro-FD), but it is continuously converted to FD by circulating active MASP-3. FD is a unique, self-inhibited protease. It has an extremely low activity toward free factor B (FB), while it is a highly efficient enzyme toward FB complexed with C3b (C3bB). The structural basis of this phenomenon is known; however, the rate enhancement was not yet quantified. It has also been unknown whether pro-FD has any enzymatic activity. In this study, we aimed to measure the activity of human FD and pro-FD toward uncomplexed FB and C3bB in order to quantitatively characterize the substrate-induced activity enhancement and zymogenicity of FD. Pro-FD was stabilized in the proenzyme form by replacing Arg25 (precursor numbering) with Gln (pro-FD-R/Q). Activated MASP-1 and MASP-3 catalytic fragments were also included in the study for comparison. We found that the complex formation with C3b enhanced the cleavage rate of FB by FD approximately 20 million-fold. C3bB was also a better substrate for MASP-1, approximately 100-fold, than free FB, showing that binding to C3b renders the scissile Arg-Lys bond in FB to become more accessible for proteolysis. Though easily measurable, this cleavage by MASP-1 is not relevant physiologically. Our approach provides quantitative data for the two-step mechanism characterized by the enhanced susceptibility of FB for cleavage upon complex formation with C3b and the substrate-induced activity enhancement of FD upon its binding to C3bB. Earlier MASP-3 was also implicated as a potential FB activator; however, MASP-3 does not cleave C3bB (or FB) at an appreciable rate. Finally, pro-FD cleaves C3bB at a rate that could be physiologically significant. The zymogenicity of FD is approximately 800, i.e., the cleavage rate of C3bB by pro-FD-R/Q was found to be approximately 800-fold lower than that by FD. Moreover, pro-FD-R/Q at approximately 50-fold of the physiological FD concentration could restore half-maximal AP activity of FD-depleted human serum on zymosan. The observed zymogen activity of pro-FD might be relevant in MASP-3 deficiency cases or during therapeutic MASP-3 inhibition.

Review on Performance of Aspergillus and Penicillium Species in Biodegradation of Organochlorine and Organophosphorus Pesticides.

The use of pesticides in agricultural practices raises concerns considering the toxic effects they generate in the environment; thus, their sustainable application in crop production remains a challenge. One of the frequently addressed issues regarding their application includes the development of a sustainable and ecofriendly approach for their degradation. Since the filamentous fungi can bioremediate various xenobiotics owing to their efficient and versatile enzymatic machinery, this review has addressed their performance in the biodegradation of organochlorine and organophosphorus pesticides. It is focused particularly on fungal strains belonging to the genera Aspergillus and Penicillium, since both are ubiquitous in the environment, and often abundant in soils contaminated with xenobiotics. Most of the recent reviews on microbial biodegradation of pesticides focus primarily on bacteria, and the soil filamentous fungi are mentioned only marginally there. Therefore, in this review, we have attempted to demonstrate and highlight the exceptional potential of aspergilli and penicillia in degrading the organochlorine and organophosphorus pesticides (e.g., endosulfan, lindane, chlorpyrifos, and methyl parathion). These biologically active xenobiotics have been degraded by fungi into various metabolites efficaciously, or these are completely mineralized within a few days. Since they have demonstrated high rates of degradation activity, as well as high tolerance to pesticides, most of the Aspergillus and Penicillium species strains listed in this review are excellent candidates for the remediation of pesticide-contaminated soils.

Involvement of Bacterial and Fungal Extracellular Products in Transformation of Manganese-Bearing Minerals and Its Environmental Impact.

Manganese oxides are considered an essential component of natural geochemical barriers due to their redox and sorptive reactivity towards essential and potentially toxic trace elements. Despite the perception that they are in a relatively stable phase, microorganisms can actively alter the prevailing conditions in their microenvironment and initiate the dissolution of minerals, a process that is governed by various direct (enzymatic) or indirect mechanisms. Microorganisms are also capable of precipitating the bioavailable manganese ions via redox transformations into biogenic minerals, including manganese oxides (e.g., low-crystalline birnessite) or oxalates. Microbially mediated transformation influences the (bio)geochemistry of manganese and also the environmental chemistry of elements intimately associated with its oxides. Therefore, the biodeterioration of manganese-bearing phases and the subsequent biologically induced precipitation of new biogenic minerals may inevitably and severely impact the environment. This review highlights and discusses the role of microbially induced or catalyzed processes that affect the transformation of manganese oxides in the environment as relevant to the function of geochemical barriers.

Evaluation of enzymatic stamp removal strategies on handmade (cellulose-based) and machine-made (lignin-containing) papers.

Two different biocleaning techniques for stamp removal from different paper samples (handmade and machine-made) were investigated. Cellulose is the main component of handmade paper, while higher concentration of lignin is present in machine-made paper. Biocleaning methods included the direct application on paper surfaces of the extracellular enzymatic mixture (EEM) extracted from the yeast Sporidiobolus metaroseus and the recombinant protein CthediskatG of Chaetomium thermophilum var. dissitum. The produced microbial enzymes (EEM or CthediskatG) were also combined with agarose hydrogels. The effectiveness of the cleaning ability of the individual methods was determined using different spectrophotometer measurements based on colorimetric analysis and by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR). Some tested samples were also subjected to microstructural and chemical analysis using Scanning Electron Microscope-Energy-Dispersive X-ray spectroscopy (SEM-EDX). The analysis showed that the EEM-based approaches were the most suitable, mainly they are less time-consuming and easy to produce, and moreover slight differences were displayed between EEM and CthediskatG during the removal of the stamp by hydrogel-enzyme approaches. Both EEM applications (direct and hydrogel) speed up the stamp removal process from real paper samples. However, for the complete elimination of the stamp smears a quick N,N-dimethylformamide post-treatment is advised too.

Prospects of Biogenic Xanthan and Gellan in Removal of Heavy Metals from Contaminated Waters.

Biosorption is considered an effective technique for the treatment of heavy-metal-bearing wastewaters. In recent years, various biogenic products, including native and functionalized biopolymers, have been successfully employed in technologies aiming for the environmentally sustainable immobilization and removal of heavy metals at contaminated sites, including two commercially available heteropolysaccharides-xanthan and gellan. As biodegradable and non-toxic fermentation products, xanthan and gellan have been successfully tested in various remediation techniques. Here, to highlight their prospects as green adsorbents for water decontamination, we have reviewed their biosynthesis machinery and chemical properties that are linked to their sorptive interactions, as well as their actual performance in the remediation of heavy metal contaminated waters. Their sorptive performance in native and modified forms is promising; thus, both xanthan and gellan are emerging as new green-based materials for the cost-effective and efficient remediation of heavy metal-contaminated waters.

Unusual perfusion patterns on perfusion-only SPECT/CT scans in COVID-19 patients.

PURPOSE: We aimed at examining both the incidence and extent of different lung perfusion abnormalities as well as the relationship between them on Tc-99m macroaggregated albumin (MAA) perfusion-only SPECT/CT scans in COVID-19 patients. METHODS: Ninety-one patients (71.4 ± 13.9 years; range: 29-98 years, median age: 74 years; 45 female and 46 male) with confirmed SARS-CoV-2 virus infection were included in this retrospective study. After performing perfusion-only Tc-99m MAA SPECT/CT scans, visual, semi-quantitative assessment of the subsequent perfusion abnormalities was carried out: mismatch lesions (MM; activity defects on SPECT images identical to apparently healthy parenchyma on CT images), matched lesions (MA; activity defects with corresponding parenchymal lesions on CT scans), and reverse mismatch lesions (RM; parenchymal lesions with preserved or increased tracer uptake). Lesion-based and patient-based analysis were performed to evaluate the extent, severity, and incidence of each perfusion abnormality. Statistical tests were applied to investigate the association between the experienced perfusion impairments. RESULTS: Moderately severe parenchymal lesions were detected in 87 (95.6%) patients. Although, 50 (54.95%) patients were depicted to have MM lesions, the whole patient cohort was mildly affected by this abnormality. MA lesions of average moderate severity were seen in most of the patients (89.01%). In 65 (71.43%) patients RM lesions were found with mild severity on average. Positive association was detected between total CT score and total RM score and between total CT score and total MA score. Significantly higher total CT scores were experienced in the subgroup, where RM lesions were present. CONCLUSIONS: Heterogeneous perfusion abnormalities were found in most of COVID-19 patients: parenchymal lesions with normal, decreased or increased perfusion and perfusion defects in healthy lung areas. These phenomena may be explained by the failure of the hypoxic pulmonary vasoconstriction mechanism and presence of pulmonary thrombosis and embolism.

A Process-Oriented View of Procedural Memory Can Help Better Understand Tourette's Syndrome.

Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by repetitive movements and vocalizations, also known as tics. The phenomenology of tics and the underlying neurobiology of the disorder have suggested that the altered functioning of the procedural memory system might contribute to its etiology. However, contrary to the robust findings of impaired procedural memory in neurodevelopmental disorders of language, results from TS have been somewhat mixed. We review the previous studies in the field and note that they have reported normal, impaired, and even enhanced procedural performance. These mixed findings may be at least partially be explained by the diversity of the samples in both age and tic severity, the vast array of tasks used, the low sample sizes, and the possible confounding effects of other cognitive functions, such as executive functions, working memory or attention. However, we propose that another often overlooked factor could also contribute to the mixed findings, namely the multiprocess nature of the procedural system itself. We propose that a process-oriented view of procedural memory functions could serve as a theoretical framework to help integrate these varied findings. We discuss evidence suggesting heterogeneity in the neural regions and their functional contributions to procedural memory. Our process-oriented framework can help to deepen our understanding of the complex profile of procedural functioning in TS and atypical development in general.

Bioleaching of Manganese Oxides at Different Oxidation States by Filamentous Fungus Aspergillus niger.

This work aimed to examine the bioleaching of manganese oxides at various oxidation states (MnO, MnO·Mn2O3, Mn2O3 and MnO2) by a strain of the filamentous fungus Aspergillus niger, a frequent soil representative. Our results showed that the fungus effectively disintegrated the crystal structure of selected mineral manganese phases. Thereby, during a 31-day static incubation of oxides in the presence of fungus, manganese was bioextracted into the culture medium and, in some cases, transformed into a new biogenic mineral. The latter resulted from the precipitation of extracted manganese with biogenic oxalate. The Mn(II,III)-oxide was the most susceptible to fungal biodeterioration, and up to 26% of the manganese content in oxide was extracted by the fungus into the medium. The detected variabilities in biogenic oxalate and gluconate accumulation in the medium are also discussed regarding the fungal sensitivity to manganese. These suggest an alternative pathway of manganese oxides' biodeterioration via a reductive dissolution. There, the oxalate metabolites are consumed as the reductive agents. Our results highlight the significance of fungal activity in manganese mobilization and transformation. The soil fungi should be considered an important geoactive agent that affects the stability of natural geochemical barriers.

Fungal Mobilization of Selenium in the Presence of Hausmannite and Ferric Oxyhydroxides.

Bioleaching of mineral phases plays a crucial role in the mobility and availability of various elements, including selenium. Therefore, the leachability of selenium associated with the surfaces of ferric and manganese oxides and oxyhydroxides, the prevailing components of natural geochemical barriers, has been studied in the presence of filamentous fungus. Both geoactive phases were exposed to selenate and subsequently to growing fungus Aspergillus niger for three weeks. This common soil fungus has shown exceptional ability to alter the distribution and mobility of selenium in the presence of both solid phases. The fungus initiated the extensive bioextraction of selenium from the surfaces of amorphous ferric oxyhydroxides, while the hausmannite (Mn3O4) was highly susceptible to biodeterioration in the presence of selenium. This resulted in specific outcomes regarding the selenium, iron, and manganese uptake by fungus and residual selenium concentrations in mineral phases as well. The adverse effects of bioleaching on fungal growth are also discussed.

Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder.

RATIONALE: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and restricted, repetitive behaviors. The unmet medical need in ASD is considerable since there is no approved pharmacotherapy for the treatment of these deficits in social communication, interaction, and behavior. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist, is already approved for the treatment of schizophrenia and bipolar I disorder in adults; investigation in patients with ASD is warranted. OBJECTIVES: The aim of this study was to investigate the effects of cariprazine, compared with risperidone and aripiprazole, in the rat prenatal valporic acid (VPA) exposure model on behavioral endpoints representing the core and associated symptoms of ASD. METHODS: To induce the ASD model, time-mated Wistar rat dams were treated with VPA during pregnancy. Male offspring were assigned to groups and studied in a behavioral test battery at different ages, employing social play, open field, social approach-avoidance, and social recognition memory tests. Animals were dosed orally, once a day for 8 days, with test compounds (cariprazine, risperidone, aripiprazole) or vehicle before behavioral assessment. RESULTS: Cariprazine showed dose-dependent efficacy on all behavioral endpoints. In the social play paradigm, only cariprazine was effective. On the remaining behavioral endpoints, including the reversal of hyperactivity, risperidone and aripiprazole displayed similar efficacy to cariprazine. CONCLUSIONS: In the present study, cariprazine effectively reversed core behavioral deficits and hyperactivity present in juvenile and young adult autistic-like rats. These findings indicate that cariprazine may be useful in the treatment of ASD symptoms.

Dissociation between two aspects of procedural learning in Tourette syndrome: Enhanced statistical and impaired sequence learning.

Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder that primarily affects the cortico-basal ganglia-thalamo-cortical (CBGTC) circuitry and is characterized by motor and vocal tics. Previous studies have found enhancement in procedural memory, which depends on the CBGTC circuitry and plays an important role in the learning and processing of numerous motor, social, and cognitive skills and habits. Based on these studies, procedural hyperfunctioning in TS has been proposed. However, the neurocognitive mechanism underlying such hyperfunctioning is poorly understood. Here, we investigated how two aspects of procedural learning, namely 1) frequency-based statistical learning and 2) order-based sequence learning, are affected in TS. Twenty-one children with TS between the ages of ten and fifteen as well as 21 typically developing controls were tested on a probabilistic sequence learning task that enables the parallel assessment of these two aspects. We found that children with TS showed enhanced sensitivity to statistical information but impaired sequence learning compared to typically developing children. The deconstruction of procedural memory suggests that procedural hyperfunctioning in TS may be supported by enhanced sensitivity to statistical information. These results can provide a potential path for improving therapy methods and skill-oriented educational programs for TS.

Mobilisation of hazardous elements from arsenic-rich mine drainage ochres by three Aspergillus species.

Natural ferric ochres that precipitate in streambeds at abandoned mining sites are natural scavengers of various metals and metalloids. Thus, their chemical and structural modification via microbial activity should be considered in evaluation of the risks emerging from probable spread of contamination at mining sites. Our results highlight the role of various aspergilli strains in this process via production of acidic metabolites that affect mobility and bioavailability of coprecipitated contaminants. The Mössbauer analysis revealed subtle structural changes of iron in ochres, while the elemental analysis of non-dissolved residues of ochres that were exposed to filamentous fungi suggest coinciding bioextraction of arsenic and antimony with extensive iron mobilisation. However, the zinc bioextraction by filamentous fungi is less likely dependent on iron leaching from ferric ochres. The strain specific bioextraction efficiency and subsequent bioaccumulation of mobilised metals resulted in distinct tolerance responses among the studied soil fungal strains. However, regardless the burden of bioextracted metal(loid)s on its activity, the Aspergillus niger strain has shown remarkable capability to decrease pH of its environment and, thus, bioextract significant and environmentally relevant amounts of potentially toxic elements from the natural ochres.

Synthesis of Tetravalent Thio- and Selenogalactoside-Presenting Galactoclusters and Their Interactions with Bacterial Lectin PA-IL from Pseudomonas aeruginosa.

Synthesis of tetravalent thio- and selenogalactopyranoside-containing glycoclusters using azide-alkyne click strategy is presented. Prepared compounds are potential ligands of Pseudomonas aeruginosa lectin PA-IL. P. aeruginosa is an opportunistic human pathogen associated with cystic fibrosis, and PA-IL is one of its virulence factors. The interactions of PA-IL and tetravalent glycoconjugates were investigated using hemagglutination inhibition assay and compared with mono- and divalent galactosides (propargyl 1-thio- and 1-seleno-ß-d-galactopyranoside, digalactosyl diselenide and digalactosyl disulfide). The lectin-carbohydrate interactions were also studied by saturation transfer difference NMR technique. Both thio- and seleno-tetravalent glycoconjugates were able to inhibit PA-IL significantly better than simple d-galactose or their intermediate compounds from the synthesis.

Cariprazine modulates sleep architecture in rats.

BACKGROUND: Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist compound recently introduced to treat schizophrenia and bipolar disorder. Although cariprazine is clinically classified as a low-somnolence drug, to date no detailed polysomnographic study is available on its effect on sleep. AIMS: This study examined the acute systemic effects of cariprazine on the rat sleep architecture and electroencephalography spectral power. METHODS: Sprague Dawley rats were recorded during their normal sleep period for four hours, and their sleep stages were classified. RESULTS: Cariprazine (0.3 mg/kg i.p.) reduced the time spent in rapid eye movement (REM) sleep and increased REM latency. This dose of cariprazine decreased the gamma (40-80 Hz) band frequency oscillations and increased the theta (4-9 Hz) and alpha (9-15 Hz) frequencies during the wake periods but not during slow-wave sleep. The 0.03 mg/kg dose of cariprazine only increased the alpha power during the wake periods, while the 0.003 mg/kg dose was without any effect. CONCLUSION: Taken together, the present results suggest that the REM-suppressing effect of cariprazine may be related to its effectiveness in improving depressive symptoms, as various drugs with similar REM-reducing properties effectively treat the depressive state, whereas the gamma power-reducing effect of cariprazine may be indicative of its efficacy in schizophrenia or mania, as similar effects have been observed with other D2 and 5-HT2 receptor antagonist drugs. These data contribute to our understanding of the complex mechanism of action that may stand behind the clinical efficacy of cariprazine.