Rationale: Impaired attention/vigilance is putatively core to schizophrenia. The dopaminergic D(1) receptor system has been reported as one of the most promising targets for improving cognition in patients with schizophrenia, with some evidence suggesting D(1) activation may improve sustained attention.
Objectives: The purpose of this study was twofold: firstly assessing the applicability of using rats in the 5-Choice Continuous Performance Test (5 C-CPT), recently validated in mice. Secondly, the effect of systemic administration of a D(1) partial agonist, SKF 38393, on task performance during baseline, and a challenge session consisting of a reduced event-rate was investigated.
Methods: Animals were trained to perform the 5 C-CPT with performance assessed following systemic SKF 38393 (2, 4 and 6 mg/kg) vs. vehicle administration.
Results: Rats could discriminate between target (requiring a response) and non-target (requiring the inhibition of response) trials within the 5 C-CPT. Moreover, SKF 38393 treatment impaired performance during the baseline session reducing target detection, yet improved performance during the reduced event-rate challenge session, increasing target detection and improving signal discrimination indicating an SKF 38393-induced enhancement of vigilance. Thus, these data suggest that activation of the D(1) system affected 5 C-CPT performance in a baseline dependent manner.
Conclusion: Rats can be trained to perform the 5 C-CPT, appropriately withholding from responding to non-target trials. Systemic administration of SKF 38393 impaired performance during baseline conditions. Following a task-related challenge, which reduced the event rate, activation of the dopamine (DA) D(1) system improved performance by heightening the animals' vigilance levels, quantified using signal detection theory.
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http://dx.doi.org/10.1007/s00213-011-2460-8 | DOI Listing |
J Neurosci Res
January 2025
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de Mexico, Mexico.
Lateralization of motor behavior, a common phenomenon in humans and several species, is modulated by the basal ganglia, a site pointed out for the interhemispheric differences related to lateralization. Our study aims to shed light on the potential role of the striatonigral D1 receptor in functional asymmetry in normal conditions through neurochemical and behavioral means. We found that D1 receptor activation and D1/D3 receptor coactivation in striatonigral neurons leads to more cAMP production by adenylyl cyclase in the striatum and GABA release in their terminals in the right hemisphere compared to the left.
View Article and Find Full Text PDFPharmacol Biochem Behav
January 2025
Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences, Tehran, Iran; Department of Basic Sciences, Iranian Academy of Medical Sciences, Tehran, Iran. Electronic address:
The opioidergic and dopaminergic systems play an essential role in processing pain information in the nucleus accumbens (NAc). The present work examined the hypothesis that interaction between opioidergic and D1-like dopamine receptors in the NAc area may influence acute pain-related behaviors. One hundred sixty adult male Wistar rats unilaterally received different doses of the drug solution or vehicle.
View Article and Find Full Text PDFACS Chem Neurosci
November 2024
Cancer Center and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
This study explores the intricacies of dopamine receptor-ligand interactions, focusing on the D1R and D5R subtypes. Using molecular modeling techniques, we investigated the binding of the pan-agonist rotigotine, revealing a universal binding mode at the orthosteric binding pocket. Additionally, we analyze the stability of antagonist-receptor complexes with SKF83566 and SCH23390.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
September 2024
School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong, People's Republic of China.
Gap junctions are channels that allow for direct transmission of electrical signals between cells. However, the ability of one cell to be impacted or controlled by other cells through gap junctions remains unclear. In this study, heterocellular coupling between ON α retinal ganglion cells (α-RGCs) and displaced amacrine cells (ACs) in the mouse retina was used as a model.
View Article and Find Full Text PDFJ Org Chem
February 2024
Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Key Laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, Hubei Key Laboratory of Materials Chemistry and Service Failure, and School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China.
We describe a ReO-mediated intramolecular dehydrative Friedel-Crafts reaction for the efficient synthesis of various benzo-fused heterocycles such as benzazepines and benzazocines. This process is characterized by a broad substrate scope, mild reaction conditions, high efficiency, and high atom economy. The potential application of this methodology was exemplified by the facile preparation of a NMDA antagonist as well as a key intermediate en route to SKF 38393.
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