The NIMH research domain criteria (RDoC) approach was instigated to refocus mental health research on the neural circuits that mediate psychological functions, with the idea that this would foster an understanding of the neural basis of specific psychiatric dysfunctions (i.e. 'symptoms and circuits') and ultimately facilitate treatment. As a general idea, this attempt to go beyond traditional diagnostic categories and focus on neural circuit dysfunctions related to specific symptoms spanning multiple disorders has many advantages. For example, motivational dysfunctions are present in multiple disorders, including depression, schizophrenia, Parkinson's disease, and other conditions. A critical aspect of motivation is effort valuation/willingness to work, and several clinical studies have identified alterations in effort-based decision making in various patient groups. In parallel, formal animal models focusing on the exertion of effort and effort-based decision making have been developed. This paper reviews the literature on models of effort-based motivational function in the context of a discussion of the RDoC approach, with an emphasis on the dissociable nature of distinct aspects of motivation. For example, conditions associated with depression and schizophrenia blunt the selection of high-effort activities as measured by several tasks in animal models (e.g. lever pressing, barrier climbing, wheel running). Nevertheless, these manipulations also leave fundamental aspects of hedonic reactivity, food motivation, and reinforcement intact. This pattern of effects demonstrates that the general emphasis of the RDoC on the specificity of the neural circuits mediating behavioral pathologies, and the dissociative nature of these dysfunctions, is a valid concept. Nevertheless, the specific placement of effort-related processes as simply a 'sub-construct' of 'reward processing' is empirically and conceptually problematic. Thus, while the RDoC is an excellent general framework for new ways to approach research and therapeutics, it still needs further refinement.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1042/ETLS20220008 | DOI Listing |
Sci Adv
January 2025
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Particle elasticity has widely been established to substantially influence immune cell clearance and circulation time of vascular-targeted carriers (VTCs). However, prior studies have primarily investigated interactions with macrophages, monocytic cell lines, and in vivo murine models. Interactions between particles and human neutrophils remain largely unexplored, although they represent a critical aspect of VTC performance.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Cardiac Surgery, Peking University Third Hospital, Beijing 100191, China.
Following myocardial infarction (MI), the accumulation of CD86-positive macrophages in the ischemic injury zone leads to secondary myocardial damage. Precise pharmacological intervention targeting this process remains challenging. This study engineered a nanotherapeutic delivery system with CD86-positive macrophage-specific targeting and ultrasound-responsive release capabilities.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Developmental Epileptology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Seizures elicited by corneal 6-Hz stimulation are widely acknowledged as a model of temporal lobe seizures. Despite the intensive research in rodents, no studies hint at this model in developing animals. We focused on seven age groups of both male and female rats.
View Article and Find Full Text PDFPLoS One
January 2025
Laboratório de Imunologia Celular (LIM-17), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Background: NETosis is recognized as an important source of autoantigens. Therefore, we hypothesized whether the pristane-induced lupus mice model shows early activation of neutrophils, the presence of low-density granulocytes (LDGs), and neutrophil extracellular traps (NETs) release, which could contribute to the development of a lupus phenotype.
Methods: Twelve female wild-type Balb/c mice were intraperitoneally injected with pristane (n = 6; pristane group) or saline (n = 6; control group).
PLoS One
January 2025
BioMarin Pharmaceutical Inc., Novato, CA, United States of America.
The GM2 gangliosidoses, Tay-Sachs disease and Sandhoff disease, are devastating neurodegenerative disorders caused by β-hexosaminidase A (HexA) deficiency. In the Sandhoff disease mouse model, rescue potential was severely reduced when HexA was introduced after disease onset. Here, we assess the effect of recombinant HexA and HexD3, a newly engineered mimetic of HexA optimized for the treatment of Tay-Sachs disease and Sandhoff disease.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!