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Azzam, M.

Publications and source records attributed to Azzam, M..

2 recordsLinked to original sources

Functional Connectivity Alterations in Cocaine Use Disorder: Insights from the Triple Network Model and the Addictions Neuroclinical Assessment Framework

Cocaine use disorder (CUD) disrupts functional connectivity within key brain networks, specifically the default mode network (DMN), salience network (SN), and central executive network (CEN). While the triple network model has been proposed to explain various psychiatric disorders, its applicability to CUD requires further exploration. In the present study, we built machine learning classifiers based on different combinations of DMN/SN/CEN to distinguish cocaine-use disorder (CUD) subjects from healthy control (HC) subjects. Among them, the combination of the SN and the CEN results in a remarkably high accuracy of 73.4% (sensitivity/specificity: 69.6%/78.6%, AUC: 0.78), outperforming the model based on the full triple network. This supports the hypothesis that during the binge/intoxication stage of addiction, the SN and the CEN play a more critical role than the DMN, consistent with the Addictions Neuroclinical Assessment (ANA) framework. Functional connectivity analysis revealed decreased connectivity within the DMN and the SN and increased connectivity within the CEN in CUD patients, suggesting that alterations in these networks could serve as biomarkers for addiction severity.

neuroscience↗

Toll-like receptor 3 activation increases voluntary alcohol intake in C57BL/6J male mice

Many genes differentially expressed in brain tissue from human alcoholics and animals that have consumed large amounts of alcohol are components of the innate immune toll-like receptor (TLR) pathway. TLRs initiate inflammatory responses via two branches: (1) MyD88-dependent or (2) TRIF-dependent. All TLRs signal through MyD88 except TLR3. Prior work demonstrated a direct role for MyD88-dependent signaling in regulation of alcohol consumption. However, the role of TLR3 as a potential regulator of excessive alcohol drinking has not previously been investigated. To test the possibility TLR3 activation regulates alcohol consumption, we injected mice with the TLR3 agonist polyinosinic:polycytidylic acid (poly(I:C)) and tested alcohol consumption in an every-other-day two-bottle choice test. Poly(I:C) produced a persistent increase in alcohol intake that developed over several days. Repeated poly(I:C) and ethanol exposure altered innate immune transcript abundance; increased levels of TRIF-dependent pathway components correlated with increased alcohol consumption. Administration of poly(I:C) before exposure to alcohol did not alter alcohol intake, suggesting that poly(I:C) and ethanol must be present together to change drinking behavior. To determine which branch of TLR signaling mediates poly(I:C)-induced changes in drinking behavior, we tested either mice lacking MyD88 or mice administered a TLR3/dsRNA complex inhibitor. MyD88 null mutants showed poly(I:C)-induced increases in alcohol intake. In contrast, mice pretreated with a TLR3/dsRNA complex inhibitor reduced their alcohol intake, suggesting poly(I:C)-induced escalations in alcohol intake function are, at least partially, dependent on TLR3. Together, these results strongly suggest that TLR3-dependent signaling drives excessive alcohol drinking behavior.\n\nHighlightsO_LIActivation of TLR3 via poly(I:C) increased alcohol intake.\nC_LIO_LIPoly(I:C) and ethanol must be present together to change drinking behavior.\nC_LIO_LIIncreased alcohol intake due to poly(I:C) is independent of MYD88.\nC_LIO_LIIncreased alcohol intake due to poly(I:C) is dependent on TLR3.\nC_LI

neuroscience↗