98%
921
2 minutes
20
Deficits in cognitive flexibility have been characterized in affective, anxiety, and neurodegenerative disorders. This paper reviews data, mainly from studies on animal models, that support the existence of a cortical-striatal brain circuit modulated by dopamine (DA), playing a major role in cognitive/behavioral flexibility. Moreover, we reviewed clinical findings supporting misfunctioning of this circuit in Parkinson's disease that could be responsible for some important non-motoric symptoms. The reviewed findings point to a role of catecholaminergic transmission in the medial prefrontal cortex (mpFC) in modulating DA's availability in the nucleus accumbens (NAc), as well as a role of NAc DA in modulating the motivational value of natural and conditioned stimuli. The review section is accompanied by a preliminary experiment aimed at testing weather the extinction of a simple Pavlovian association fosters increased DA transmission in the mpFC and inhibition of DA transmission in the NAc.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740496 | PMC |
http://dx.doi.org/10.3390/biomedicines11123189 | DOI Listing |
Metab Brain Dis
September 2025
Department of Physiology, Ladoke Akintola University, Ogbomoso, Oyo State, Nigeria.
Background: Acyclovir is a potent antiviral agent with variable side effects on the central nervous system. Although previous studies have shown that acyclovir has neurotoxic effects, there is a dearth of scientific information on the mechanisms through which acyclovir induces neurotoxicity.
Aim: Thus, the present study assessed the impact of acyclovir on oxidative stress, inflammatory markers, and neurotransmitter levels in the cerebellum, prefrontal cortex, and basal ganglia and its potential impact on cognition and motor function.
Biomolecules
August 2025
School of Psychological Sciences, University of Haifa, Haifa 3498838, Israel.
Cognitive flexibility, the ability to adapt behavior to changing environmental demands, is a core deficit in schizophrenia (SZ), that predicts disease progression. This review synthesizes findings on the neural substates of cognitive flexibility by using a framework that distinguishes animal model tasks by their motivational valence: aversive versus appetitive. While human studies using tasks like the Wisconsin Card Sorting Test (WCST) reveal significant cognitive inflexibility in SZ, particularly in set shifting, rodent models provide important mechanistic insights.
View Article and Find Full Text PDFFront Psychiatry
August 2025
Laboratory of Alcohology, Department of Pathology, Medical School of Crete, University of Crete, Herakleion, Greece.
Importance: Aripiprazole, a partial D2 receptor agonist, is proposed to enhance prefrontal cortex (PFC) dopamine function, improving working memory and GABA transmission, which supports social functioning. Long-acting injectable (LAI) antipsychotics are known to improve patient adherence, leading to enhanced long-term effects on behavioral outcomes.
Objective: To evaluate whether aripiprazole LAI treatment improves general functioning, quality of life, and reduces hospitalizations in psychotic patients, both in community settings and within incarcerated populations.
Med Sci (Basel)
August 2025
Emergency Service, GHOL Hôpital de Nyon, 1260 Nyon, Switzerland.
Substance use disorders (SUDs) remain a major public health challenge, with existing pharmacotherapies offering limited long-term efficacy. Traditional treatments focus on dopaminergic systems but often overlook the complex interplay between metabolic signals, neuroplasticity, and conditioned behaviors that perpetuate addiction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, have recently emerged as promising modulators of reward-related brain circuits.
View Article and Find Full Text PDFNeuropharmacology
November 2025
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, 77807, United States. Electronic address:
Relapse remains a major challenge in the treatment of alcohol use disorder, driven in part by persistent neuroadaptations. However, how different post-alcohol experiences, such as passive withdrawal (abstinence) versus active extinction training, differentially shape the neural circuits and synaptic mechanisms that influence relapse vulnerability remains unclear. Here, we show that these experiences have opposing effects on dorsomedial striatal (DMS) direct-pathway medium spiny neurons (dMSNs) and dopamine dynamics during cue-induced reinstatement of alcohol seeking.
View Article and Find Full Text PDF