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Repeated forced swim exacerbates methamphetamine-induced neurotoxicity: Neuroprotective effects of nanowired delivery of 5-HT3-receptor antagonist ondansetron

dc.contributor.authorLafuente J.V.
dc.contributor.authorSharma A.
dc.contributor.authorMuresanu D.F.
dc.contributor.authorOzkizilcik A.
dc.contributor.authorTian Z.R.
dc.contributor.authorPatnaik R.
dc.contributor.authorSharma H.S.
dc.date.accessioned2020-09-02T22:21:11Z
dc.date.available2020-09-02T22:21:11Z
dc.date.issued2018
dc.identifier10.1007/s12035-017-0744-7
dc.identifier.citation55, 1, 322-334
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5023
dc.descriptionThe possibility that stress associated with chronic forced swim (FS) may exacerbate methamphetamine (METH) neurotoxicity was examined in a rat model. Rats were subjected to FS in a pool (30 °C) for 15 min daily for 8 days. Control rats were kept at room temperature. METH was administered (9 mg/kg, s.c.) in both control and FS rats and allowed to survive 4 h after the drug injection. METH in FS rats exacerbated BBB breakdown to Evans blue albumin (EBA) by 150 to 220% and[131]-Iodine by 250 to 380% as compared to naive rats after METH. The METH-induced BBB leakage was most pronounced in the cerebral cortex followed by the hippocampus, cerebellum, thalamus, and hypothalamus in both FS and naive rats. The regional BBB changes were associated with a reduction in the local cerebral blood flow (CBF). Brain edema was also higher by 2 to 4% in FS rats after METH than in naive animals. Neuronal and glial cell injuries were aggravated by threefold to fivefold after METH in FS than the control group. Pretreatment with ondansetron (1 mg/kg, i.p.) 30 min before METH injection in naive rats reduced the brain pathology and improved the CBF. However, TiO2-nanowired delivery of ondansetron (1 mg/kg, i.p.) was needed to reduce METH-induced brain damage, BBB leakage, reduction in CBF, and edema formation in FS. Taken together, these observations are the first to show that METH exacerbates BBB breakdown leading to neurotoxicity in FS animals. This effect of METH-induced BBB breakdown and brain pathology in naive and FS rats is attenuated by ondansetron treatment indicating an involvement of 5-HT3 receptors, not reported earlier. © Springer Science+Business Media New York 2016.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subject5-HT3 receptor
dc.subjectBlood-brain barrier (BBB)
dc.subjectBrain edema
dc.subjectBrain pathology
dc.subjectForced swim (FS)
dc.subjectMethamphetamine (METH)
dc.subjectOndansetron
dc.subjectTiO2 nanodelivery
dc.subjectalbumin
dc.subjectEvans blue
dc.subjectmethamphetamine
dc.subjectnanowire
dc.subjectondansetron
dc.subjecttitanium dioxide
dc.subjectnanowire
dc.subjectneuroprotective agent
dc.subjectondansetron
dc.subjectserotonin 3 antagonist
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectbrain blood flow
dc.subjectbrain damage
dc.subjectbrain edema
dc.subjectcell activation
dc.subjectcerebellum
dc.subjectcontrolled study
dc.subjectdrug delivery system
dc.subjectforced swim test
dc.subjectglia cell
dc.subjecthippocampus
dc.subjecthypothalamus
dc.subjectmale
dc.subjectneuroprotection
dc.subjectneurotoxicity
dc.subjectnonhuman
dc.subjectrat
dc.subjectsurvival
dc.subjectthalamus
dc.subjectanimal
dc.subjectblood brain barrier
dc.subjectbrain
dc.subjectbrain edema
dc.subjectchemically induced
dc.subjectdrug effect
dc.subjectpathology
dc.subjectprocedures
dc.subjectpsychology
dc.subjectSprague Dawley rat
dc.subjectswimming
dc.subjectAnimals
dc.subjectBlood-Brain Barrier
dc.subjectBrain
dc.subjectBrain Edema
dc.subjectDrug Delivery Systems
dc.subjectMale
dc.subjectMethamphetamine
dc.subjectNanowires
dc.subjectNeuroprotective Agents
dc.subjectOndansetron
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectSerotonin 5-HT3 Receptor Antagonists
dc.subjectSwimming
dc.titleRepeated forced swim exacerbates methamphetamine-induced neurotoxicity: Neuroprotective effects of nanowired delivery of 5-HT3-receptor antagonist ondansetron
dc.typeArticle


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