This study examined the effects of two chronic stress regimens upon depressive-like behavior, A(1) and A(2A) adenosine receptor binding and immunocontent. Male rats were subjected to unpredictable chronic mild stress (UCMS) or to chronic restraint stress (CRS) for 40 days. Subsequently, depressive-like behaviors (forced swimming and consumption of sucrose) were evaluated, and A(1) adenosine or A(2A) adenosine receptors were examined in the hippocampus or striatum, respectively. UCMS animals demonstrated depressive-related behaviors (decrease in sucrose consumption and increased immobility in the forced swimming test). This group also presented increased A(1) adenosine receptor binding and immunoreactivity in hippocampus, as well as increased striatal A(2A) adenosine receptor binding in the striatum, without alteration in immunoreactivity. Conversely, the chronic restraint stress group displayed only an increase in A(1) adenosine receptor binding and no alteration in the other parameters evaluated. We suggest that the alteration in adenosine receptors, particularly the upregulation of striatal A(2A) adenosine receptors following UCMS, could be associated with depressive-related behavior.
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http://dx.doi.org/10.1016/j.physbeh.2012.11.001 | DOI Listing |
iScience
January 2025
Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan.
Drugs that interact with multiple therapeutic targets are potential high-value products in polypharmacology-based drug discovery, but the rational design remains a formidable challenge. Here, we present artificial intelligence (AI)-based methods to design the chemical structures of compounds that interact with multiple therapeutic target proteins. The molecular structure generation is performed by a fragment-based approach using a genetic algorithm with chemical substructures and a deep learning approach using reinforcement learning with stochastic policy gradients in the framework of generative adversarial networks.
View Article and Find Full Text PDFNeurochem Res
January 2025
Department of Biochemistry and Molecular Biology, Federal University of Santa Maria (UFSM), Santa Maria, RS, Brazil.
Purinergic signaling plays a major role in aging and neurodegenerative diseases, which are associated with memory decline. Blackcurrant (BC), an anthocyanin-rich berry, is renowned for its antioxidant and neuroprotective activities. However, evidence on the effects of BC on purinergic signaling is lacking.
View Article and Find Full Text PDFActa Pharmacol Sin
January 2025
Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Joint International Research Laboratory of Sleep, Fudan University, Shanghai, 200032, China.
Adenosine A receptor (AR) plays a pivotal role in the regulation of sleep-wake behaviors. We previously reported an AR selective antagonist compound 38 with an IC value of 29.0 nM.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
CEITEC─Central European Institute of Technology, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic.
All-atom molecular dynamics simulations are powerful tools for studying cell membranes and their interactions with proteins and other molecules. However, these processes occur on time scales determined by the diffusion rate of phospholipids, which are challenging to achieve in all-atom models. Here, we present a new all-atom model that accelerates lipid diffusion by splitting phospholipid molecules into head and tail groups.
View Article and Find Full Text PDFEur J Neurosci
January 2025
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
In corticostriatal nerve terminals, glutamate release is stimulated by adenosine via A receptors (ARs) and simultaneously inhibited by endocannabinoids via CB receptors (CBRs). We previously identified presynaptic AR-CBR heterotetrameric complexes in corticostriatal nerve terminals. We now explored the possible functional interaction between ARs and CBRs in purified striatal GABAergic nerve terminals (synaptosomes) and compared these findings with those on the release of glutamate.
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