{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:25:50Z","timestamp":1759883150711,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"],"award-info":[{"award-number":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"]}]},{"name":"RISE Program","award":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"],"award-info":[{"award-number":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"]}]},{"name":"PR-INBRE Developmental Research Project Program","award":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"],"award-info":[{"award-number":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"]}]},{"name":"RCMI-Supplement Project","award":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"],"award-info":[{"award-number":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"]}]},{"name":"Catalyzer Research Grants Program","award":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"],"award-info":[{"award-number":["1F31DA05481-01A1","RCMI MD007579","R25GM082406","P20 GM103475-19","NIMHD 3U54MD007579-37S1","CRG-2020-00114"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Cocaine use disorder is an intersecting issue in populations with HIV-1, further exacerbating the clinical course of the disease and contributing to neurotoxicity and neuroinflammation. Cocaine and HIV neurotoxins play roles in neuronal damage during neuroHIV progression by disrupting glutamate homeostasis in the brain. Even with combined antiretroviral therapy (cART), HIV-1 Nef, an early viral protein expressed in approximately 1% of infected astrocytes, remains a key neurotoxin. This study investigates the relationship among Nef, glutamate homeostasis, and cocaine in the nucleus accumbens (NAc), a critical brain region associated with drug motivation and reward. Methods: Male and female Sprague Dawley rats were used to compare the effects of astrocytic Nef and cocaine by molecular analysis of glutamate transporters, GLT-1 and the cysteine glutamate exchanger (xCT), in the NAc. Behavioral assessments for cocaine self-administration were used to evaluate cocaine-seeking behavior. Results: The findings indicate that both cocaine and Nef independently decrease the expression of the glutamate transporter GLT-1 in the NAc. Additionally, rats with astrocytic Nef expression exhibited increased cocaine-seeking behavior but demonstrated sex-dependent molecular differences after the behavioral paradigm. Conclusions: The results suggest that the expression of Nef intensifies cocaine-induced alterations in glutamate homeostasis in the NAc, potentially underlying increased cocaine-seeking behavior. Understanding these interactions better may inform therapeutic strategies for managing cocaine use disorder in HIV-infected individuals.<\/jats:p>","DOI":"10.3390\/ph18010040","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T11:24:19Z","timestamp":1735730659000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocytic HIV-1 Nef Expression Decreases Glutamate Transporter Expression in the Nucleus Accumbens and Increases Cocaine-Seeking Behavior in Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Jessalyn","family":"Pla-Tenorio","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6579-9590","authenticated-orcid":false,"given":"Bethzaly","family":"Velazquez-Perez","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00716, USA"},{"name":"Department of Biomedical Sciences, Pontifical Catholic University of Puerto Rico, Ponce, PR 00717, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yainira","family":"Mendez-Borrero","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00716, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myrella L.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00716, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian T.","family":"Sepulveda-Orengo","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00716, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0467-3777","authenticated-orcid":false,"suffix":"Jr.","given":"Richard J.","family":"Noel","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00716, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"ref_1","unstructured":"(2024, May 03). Centers for Disease Control and Prevention: HIV Surveillance Report, Available online: http:\/\/www.cdc.gov\/hiv\/library\/reports\/hiv-surveillance.html."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Samji, H., Cescon, A., Hogg, R.S., Modur, S.P., Althoff, K.N., Buchacz, K., Burchell, A.N., Cohen, M., Gebo, K.A., and Gill, M.J. (2013). Closing the gap: Increases in life expectancy among treated HIV-positive individuals in the United States and Canada. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081355"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e207954","DOI":"10.1001\/jamanetworkopen.2020.7954","article-title":"Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000-2016","volume":"3","author":"Marcus","year":"2020","journal-title":"JAMA Netw Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1136\/jnnp.69.3.376","article-title":"Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART)","volume":"69","author":"Maschke","year":"2000","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/sj.cdd.4401623","article-title":"HIV-1 infection and AIDS: Consequences for the central nervous system","volume":"12","author":"Kaul","year":"2005","journal-title":"Cell Death Differ."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1097\/QAI.0b013e3181f9c04c","article-title":"HIV among people who use drugs: A global perspective of populations at risk","volume":"55","author":"Stockman","year":"2010","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1007\/s10461-016-1584-6","article-title":"Prevalence and Predictors of Substance Use Disorders Among HIV Care Enrollees in the United States","volume":"21","author":"Hartzler","year":"2017","journal-title":"AIDS Behav."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.2105\/AJPH.2012.301162","article-title":"Substance Use Among HIV-Infected Patients Engaged in Primary Care in the United States: Findings From the Centers for AIDS Research Network of Integrated Clinical Systems Cohort","volume":"103","author":"Mimiaga","year":"2013","journal-title":"Am. J. Public Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s10461-011-0124-7","article-title":"Association between use of specific drugs and antiretroviral adherence: Findings from MACH 14","volume":"17","author":"Rosen","year":"2013","journal-title":"AIDS Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1007\/s13365-021-00965-1","article-title":"Effects of cocaine and HIV on decision-making abilities","volume":"27","author":"Nigro","year":"2021","journal-title":"J. Neurovirol"},{"key":"ref_11","unstructured":"National Institute on Drug Abuse (2020). Common Comorbidities with Substance Use Disorders Research Report, National Institutes on Drug Abuse (US)."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108815","DOI":"10.1016\/j.neuropharm.2021.108815","article-title":"Assessing combinatorial effects of HIV infection and former cocaine dependence on cognitive control processes: A functional neuroimaging study of response inhibition","volume":"203","author":"Wakim","year":"2022","journal-title":"Neuropharmacology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dash, S., Balasubramaniam, M., Villalta, F., Dash, C., and Pandhare, J. (2015). Impact of cocaine abuse on HIV pathogenesis. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.01111"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mahmoud, S., Gharagozloo, M., Simard, C., and Gris, D. (2019). Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release. Cells, 8.","DOI":"10.3390\/cells8020184"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","article-title":"Astrocytes: Biology and pathology","volume":"119","author":"Sofroniew","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/B978-0-12-385506-0.00009-0","article-title":"Glutamatergic neuroplasticity in cocaine addiction","volume":"98","author":"Uys","year":"2011","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1124\/pr.116.012484","article-title":"The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis","volume":"68","author":"Scofield","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2542","DOI":"10.1038\/cddis.2016.467","article-title":"HIV-1 Nef is released in extracellular vesicles derived from astrocytes: Evidence for Nef-mediated neurotoxicity","volume":"8","author":"Cicalese","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/ana.21697","article-title":"Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia","volume":"66","author":"Churchill","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ferdin, J., Gori\u010dar, K., Dol\u017ean, V., Plemenita\u0161, A., Martin, J.N., Peterlin, B.M., Deeks, S.G., and Lenassi, M. (2018). Viral protein Nef is detected in plasma of half of HIV-infected adults with undetectable plasma HIV RNA. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191613"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cheney, L., Guzik, H., Macaluso, F.P., Macian, F., Cuervo, A.M., and Berman, J.W. (2020). HIV Nef and Antiretroviral Therapy Have an Inhibitory Effect on Autophagy in Human Astrocytes that May Contribute to HIV-Associated Neurocognitive Disorders. Cells, 9.","DOI":"10.3390\/cells9061426"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1097\/00002030-199912030-00004","article-title":"Stable expression of HIV-1 Nef induces changes in growth properties and activation state of human astrocytes","volume":"13","author":"Kohleisen","year":"1999","journal-title":"Aids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"42136","DOI":"10.1074\/jbc.M200862200","article-title":"The HIV-1 Nef protein and phagocyte NADPH oxidase activation","volume":"277","author":"Vilhardt","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/path.2276","article-title":"Immune activation and inflammation in HIV-1 infection: Causes and consequences","volume":"214","author":"Appay","year":"2008","journal-title":"J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15303","DOI":"10.1074\/jbc.271.26.15303","article-title":"Tumor necrosis factor alpha inhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia","volume":"271","author":"Fine","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1007\/s12035-015-9094-5","article-title":"Role of Sigma Receptor in Cocaine-Mediated Induction of Glial Fibrillary Acidic Protein: Implications for HAND","volume":"53","author":"Yang","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2174\/157016212802138823","article-title":"Cocaine and HIV-1 interplay in CNS: Cellular and molecular mechanisms","volume":"10","author":"Buch","year":"2012","journal-title":"Curr. HIV Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Testen, A., Sepulveda-Orengo, M.T., Gaines, C.H., and Reissner, K.J. (2018). Region-Specific Reductions in Morphometric Properties and Synaptic Colocalization of Astrocytes Following Cocaine Self-Administration and Extinction. Front. Cell Neurosci., 12.","DOI":"10.3389\/fncel.2018.00246"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1007\/s00018-015-1937-8","article-title":"Glutamate transporter EAAT2: Regulation, function, and potential as a therapeutic target for neurological and psychiatric disease","volume":"72","author":"Takahashi","year":"2015","journal-title":"Cell Mol. Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nn1069","article-title":"Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse","volume":"6","author":"Baker","year":"2003","journal-title":"Nat. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00726-001-0122-6","article-title":"Cystine\/glutamate exchange serves as the source for extracellular glutamate: Modifications by repeated cocaine administration","volume":"23","author":"Baker","year":"2002","journal-title":"Amino Acids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.nbd.2012.08.007","article-title":"Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory","volume":"49","author":"Chompre","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rivera, J., Isidro, R.A., Loucil-Alicea, R.Y., Cruz, M.L., Appleyard, C.B., Isidro, A.A., Chompre, G., Colon-Rivera, K., and Noel, R.J. (2019). Infusion of HIV-1 Nef-expressing astrocytes into the rat hippocampus induces enteropathy and interstitial pneumonitis and increases blood-brain-barrier permeability. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225760"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s13365-015-0398-z","article-title":"The effects of cocaine on HIV transcription","volume":"22","author":"Tyagi","year":"2016","journal-title":"J. Neurovirol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s13365-015-0403-6","article-title":"Decreased glial and synaptic glutamate uptake in the striatum of HIV-1 gp120 transgenic mice","volume":"22","author":"Melendez","year":"2016","journal-title":"J. Neurovirol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1046\/j.1471-4159.1998.70041497.x","article-title":"Repeated cocaine administration alters extracellular glutamate in the ventral tegmental area","volume":"70","author":"Kalivas","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrn2515","article-title":"The glutamate homeostasis hypothesis of addiction","volume":"10","author":"Kalivas","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1093\/ijnp\/pyx050","article-title":"Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse","volume":"20","author":"Spencer","year":"2017","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9239","DOI":"10.1523\/JNEUROSCI.1746-09.2009","article-title":"Upregulation of GLT1 attenuates cue-induced reinstatement of cocaine-seeking behavior in rats","volume":"29","author":"Sari","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16093","DOI":"10.1523\/JNEUROSCI.1267-14.2014","article-title":"Regulation of hippocampal synaptic strength by glial xCT","volume":"34","author":"Williams","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1089\/ars.2011.4391","article-title":"The cystine\/glutamate antiporter system x(c)(-) in health and disease: From molecular mechanisms to novel therapeutic opportunities","volume":"18","author":"Lewerenz","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/cne.903380209","article-title":"The patterns of afferent innervation of the core and shell in the \u201caccumbens\u201d part of the rat ventral striatum: Immunohistochemical detection of retrogradely transported fluoro-gold","volume":"338","author":"Brog","year":"1993","journal-title":"J. Comp. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.neuropharm.2008.06.042","article-title":"Differential cocaine-induced modulation of glutamate and dopamine transporters after contingent and non-contingent administration","volume":"55","author":"Miguens","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00213-010-1890-z","article-title":"Extracellular fluctuations of dopamine and glutamate in the nucleus accumbens core and shell associated with lever-pressing during cocaine self-administration, extinction, and yoked cocaine administration","volume":"211","author":"Suto","year":"2010","journal-title":"Psychopharmacology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"19599","DOI":"10.1074\/jbc.M114.567644","article-title":"Astrocyte elevated gene-1 is a novel modulator of HIV-1-associated neuroinflammation via regulation of nuclear factor-kappaB signaling and excitatory amino acid transporter-2 repression","volume":"289","author":"Gelman","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s11481-010-9205-z","article-title":"HIV-associated neurocognitive disorder: Pathogenesis and therapeutic opportunities","volume":"5","author":"Lindl","year":"2010","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"152","DOI":"10.14336\/AD.2022.0712","article-title":"HIV Nef Expression Down-modulated GFAP Expression and Altered Glutamate Uptake and Release and Proliferation in Astrocytes","volume":"14","author":"Wilson","year":"2023","journal-title":"Aging Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s11481-015-9594-0","article-title":"Increased Sensitivity to Cocaine Self-Administration in HIV-1 Transgenic Rats is Associated with Changes in Striatal Dopamine Transporter Binding","volume":"10","author":"McIntosh","year":"2015","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/npp.2013.201","article-title":"Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice","volume":"39","author":"Paris","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.neuroscience.2012.02.049","article-title":"Differential effects of cocaine access and withdrawal on glutamate type 1 transporter expression in rat nucleus accumbens core and shell","volume":"210","author":"Houston","year":"2012","journal-title":"Neuroscience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.biopsych.2009.07.018","article-title":"Ceftriaxone restores glutamate homeostasis and prevents relapse to cocaine seeking","volume":"67","author":"Knackstedt","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.1523\/JNEUROSCI.3717-16.2017","article-title":"Contrasting the Role of xCT and GLT-1 Upregulation in the Ability of Ceftriaxone to Attenuate the Cue-Induced Reinstatement of Cocaine Seeking and Normalize AMPA Receptor Subunit Expression","volume":"37","author":"LaCrosse","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1038\/npp.2017.244","article-title":"Riluzole Impairs Cocaine Reinstatement and Restores Adaptations in Intrinsic Excitability and GLT-1 Expression","volume":"43","author":"Healey","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.bbr.2017.06.017","article-title":"Modulatory effects of Ampicillin\/Sulbactam on glial glutamate transporters and metabotropic glutamate receptor 1 as well as reinstatement to cocaine-seeking behavior","volume":"332","author":"Hammad","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s11154-013-9263-7","article-title":"Estrogen, astrocytes and the neuroendocrine control of metabolism","volume":"14","author":"Morselli","year":"2013","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1046\/j.0022-3042.2002.00779.x","article-title":"Effects of estrogen treatment on glutamate uptake in cultured human astrocytes derived from cortex of Alzheimer's disease patients","volume":"80","author":"Liang","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s12640-012-9347-2","article-title":"Estrogen attenuates manganese-induced glutamate transporter impairment in rat primary astrocytes","volume":"23","author":"Lee","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8867","DOI":"10.1073\/pnas.1103833108","article-title":"Neuroprotection mediated through estrogen receptor-alpha in astrocytes","volume":"108","author":"Spence","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molbrainres.2004.10.043","article-title":"Regulation of glutamate transporter GLAST and GLT-1 expression in astrocytes by estrogen","volume":"138","author":"Pawlak","year":"2005","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1523\/JNEUROSCI.1432-21.2022","article-title":"Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism","volume":"42","author":"Yang","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.biopsych.2005.04.046","article-title":"Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use","volume":"58","author":"Ferrario","year":"2005","journal-title":"Biol. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3109\/13550280009015821","article-title":"Simian immunodeficiency virus mac251 infection of astrocytes","volume":"6","author":"Guillemin","year":"2000","journal-title":"J. Neurovirol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1046\/j.1365-2990.2003.00475.x","article-title":"Relationship of Nef-positive and GFAP-reactive astrocytes to drug use in early and late HIV infection","volume":"29","author":"Anderson","year":"2003","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuropharm.2017.09.019","article-title":"Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal","volume":"128","author":"Kim","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/0091-3057(87)90361-3","article-title":"One injection of cocaine produces a long-lasting increase in [3H]-dopamine release","volume":"27","author":"Peris","year":"1987","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_66","first-page":"94","article-title":"Role of monoamine systems in activation of zif268 by cocaine","volume":"17","author":"Bhat","year":"1992","journal-title":"J. Psychiatry Neurosci."},{"key":"ref_67","first-page":"486","article-title":"Involvement of N-methyl-D-aspartate receptor stimulation in the ventral tegmental area and amygdala in behavioral sensitization to cocaine","volume":"267","author":"Kalivas","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0896-6273(03)00021-7","article-title":"Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons","volume":"37","author":"Saal","year":"2003","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.biopsych.2017.03.014","article-title":"Rapid Synaptogenesis in the Nucleus Accumbens Is Induced by a Single Cocaine Administration and Stabilized by Mitogen-Activated Protein Kinase Interacting Kinase-1 Activity","volume":"82","author":"Salery","year":"2017","journal-title":"Biol. Psychiatry"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/1\/40\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T15:23:05Z","timestamp":1759850585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/1\/40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ph18010040"],"URL":"https:\/\/doi.org\/10.3390\/ph18010040","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}