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The magnitude of dopamine signals elicited by rewarding events and their predictors is updated when reward value changes. It is actively debated how readily these dopamine signals adapt and whether adaptation aligns with model-free or model-based reinforcement-learning principles. To investigate this, we trained male rats in a pavlovian-conditioning paradigm and measured dopamine release in the nucleus accumbens core in response to food reward (unconditioned stimulus) and reward-predictive conditioned stimuli (CS), both before and after reward devaluation, induced via either sensory-specific or nonspecific satiety. We demonstrate that (1) such devaluation reduces CS-induced dopamine release rapidly, without additional pairing of CS with devalued reward and irrespective of whether the devaluation was sensory-specific or nonspecific. In contrast, (2) reward devaluation did not decrease food reward-induced dopamine release. Surprisingly, (3) postdevaluation reconditioning, by additional pairing of CS with devalued reward, rapidly reinstated CS-induced dopamine signals to predevaluation levels. Taken together, we identify distinct, divergent adaptations in dopamine-signal magnitude when reward value is decreased: CS dopamine diminishes but reinstates fast, whereas reward dopamine is resistant to change. This implies that, respective to abovementioned findings, (1) CS dopamine may be governed by a model-based mechanism and (2) reward dopamine by a model-free one, where (3) the latter may contribute to swift reinstatement of the former. However, changes in CS dopamine were not selective for sensory specificity of reward devaluation, which is inconsistent with model-based processes. Thus, mesolimbic dopamine signaling incorporates both model-free and model-based mechanisms and is not exclusively governed by either.
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http://dx.doi.org/10.1523/ENEURO.0223-24.2024 | DOI Listing |
Neuropharmacology
September 2025
Department of Biochemistry, Universidade Federal do Paraná, Curitiba, PR 81.530-980, Brazil; Department of Pharmacology, Universidade Federal do Paraná, Curitiba, PR 81.530-980, Brazil. Electronic address:
Currently there is no pharmacological treatment for cocaine use disorder. Previous studies have shown that progesterone can mitigate the behavioral effects induced by cocaine in both animal models and humans. However, the underlying mechanisms through which progesterone exerts this effect remain poorly understood.
View Article and Find Full Text PDFDrug Alcohol Depend
August 2025
Center for Substance Abuse Research and Department of Neural Sciences, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA 19140, USA. Electronic address:
Background: The use of methamphetamine has continued to rise in the US. In addition to facilitating dopamine neurotransmission, methamphetamine indirectly increases glutamate release, which activates N-methyl-D-aspartate receptors (NMDARs). Ketamine is a noncompetitive NMDAR antagonist.
View Article and Find Full Text PDFACS Sens
September 2025
College of Chemistry, Beijing Normal University, Beijing 100875, China.
Dopamine (DA) signaling is essential for neurodevelopment and is particularly sensitive to disruption during adolescence. Protein restriction (PR) can impair DA dynamics, yet mechanistic insights remain limited due to challenges in real-time neurochemical sensing. Here, we present aptCFE, a robust implantable aptamer-based sensor fabricated via a reagent-free, 3 min electrochemical conjugation (E-conjugation) using amine-quinone chemistry.
View Article and Find Full Text PDFAdv Emerg Nurs J
September 2025
Author Affiliations: Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina (Dr Weant); and Department of Pharmacy, University of North Carolina Health, Chapel Hill, North Carolina (Dr Gregory).
Migraine is an often-disabling condition and a common presentation to the Emergency Department (ED). Rapid and effective treatment are essential to reduce symptom burden, prevent recurrence, and improve patient outcomes. This review provides a comprehensive, evidence-based overview of the pharmacologic management of acute migraine in the ED, including first-line therapies, rescue medications, adjunctive care strategies, and considerations for special populations.
View Article and Find Full Text PDFACS Electrochem
September 2025
Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Kemigården 4, Gothenburg 412 96, Sweden.
Carbon fiber nanotip electrodes (CFNEs) are crucial for electrochemical recordings of neurotransmission release in confined spaces, such as synapses and intracellular measurements. However, fabricating CFNEs with small surface area to minimize noise remains challenging due to inconsistent tip size control, low reproducibility, and low fabrication success rate. Here, we present a reliable, user-friendly method with high reproducibility and success rate for precise CFNE fabrication using microscopy-guided electrochemical etching of cylindrical carbon fiber microelectrodes in a potassium hydroxide droplet.
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