Differential Effects of Environment-Induced Changes in Body Temperature on Modafinil’s Actions Against Methamphetamine-Induced Striatal Toxicity in Mice
Methamphetamine (METH) exposure can produce hyperthermia that might lead to toxicity and death. Modafinil is a wake-promoting compound that is also been prescribed off-label to treat METH dependence. Modafinil has shown neuroprotective properties against METH harmful effects in animal models. The go...
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2015
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10298428_v27_n1_p71_Raineri http://hdl.handle.net/20.500.12110/paper_10298428_v27_n1_p71_Raineri |
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paper:paper_10298428_v27_n1_p71_Raineri2023-06-08T16:00:20Z Differential Effects of Environment-Induced Changes in Body Temperature on Modafinil’s Actions Against Methamphetamine-Induced Striatal Toxicity in Mice Astroglia Dopamine Methamphetamine Modafinil Striatum Toxicity dopamine transporter glial fibrillary acidic protein methamphetamine modafinil placebo protein c fos tyrosine 3 monooxygenase benzhydryl derivative dopamine receptor stimulating agent methamphetamine modafinil neuroprotective agent animal cell animal experiment animal model animal tissue Article body temperature disorder body temperature measurement cell nucleus cellular distribution controlled study corpus striatum correlational study disease marker down regulation drug protein binding drug targeting environmental exposure environmental temperature female hyperthermia immunohistochemistry immunoreactivity mouse mouse model neuropharmacology neuroprotection neurotoxicity nonhuman priority journal protein determination protein expression protein localization thermal exposure thermoregulation tissue distribution upregulation animal C57BL mouse chemically induced cold cytology drug effects heat hypothermia metabolism neostriatum nerve cell Animals Benzhydryl Compounds Cold Temperature Dopamine Agents Dopamine Plasma Membrane Transport Proteins Female Hot Temperature Hypothermia Methamphetamine Mice Mice, Inbred C57BL Neostriatum Neurons Neuroprotective Agents Proto-Oncogene Proteins c-fos Tyrosine 3-Monooxygenase Methamphetamine (METH) exposure can produce hyperthermia that might lead to toxicity and death. Modafinil is a wake-promoting compound that is also been prescribed off-label to treat METH dependence. Modafinil has shown neuroprotective properties against METH harmful effects in animal models. The goal of the present study was to test if the prevention of hyperthermia might play a role on the neuroprotective actions of modafinil against METH toxicity using various ambient temperatures. METH was administered to female C57BL/6 mice in a binge regimen: 4 × 5 mg/kg, 2 h apart; modafinil (90 mg/kg) was injected twice, 1 h before first and fourth METH injections. Drugs were given at cold ambient temperature (14 °C) or hot ambient temperature (29 °C). Body temperature was measured during treatments. Brains were dissected out 6 days after treatments and processed for tyrosine hydroxylase (TH), dopamine transporter (DAT), GFAP and c-Fos immunohistochemistry. Exposure to hot ambient temperature exacerbated METH toxicity evidenced by striatal reductions in TH and DAT and increased GFAP immmunoreactivity. Modafinil counteracted reductions in TH and DAT, but failed to block astroglial activation. At both ambient temperatures tested modafinil did induce increments in GFAP, but the magnitude was significantly lower than the one induced by METH. Both drugs induced increases in c-Fos positive nuclei; modafinil did not block this effect. Our results suggest that protective effects of modafinil against METH-induced neurotoxicity may be dependent, in part, to its hypothermic effects. Nevertheless, modafinil maintained some protective properties on METH-induced alterations in the striatum at different ambient temperatures. © 2014, Springer Science+Business Media New York. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10298428_v27_n1_p71_Raineri http://hdl.handle.net/20.500.12110/paper_10298428_v27_n1_p71_Raineri |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Astroglia Dopamine Methamphetamine Modafinil Striatum Toxicity dopamine transporter glial fibrillary acidic protein methamphetamine modafinil placebo protein c fos tyrosine 3 monooxygenase benzhydryl derivative dopamine receptor stimulating agent methamphetamine modafinil neuroprotective agent animal cell animal experiment animal model animal tissue Article body temperature disorder body temperature measurement cell nucleus cellular distribution controlled study corpus striatum correlational study disease marker down regulation drug protein binding drug targeting environmental exposure environmental temperature female hyperthermia immunohistochemistry immunoreactivity mouse mouse model neuropharmacology neuroprotection neurotoxicity nonhuman priority journal protein determination protein expression protein localization thermal exposure thermoregulation tissue distribution upregulation animal C57BL mouse chemically induced cold cytology drug effects heat hypothermia metabolism neostriatum nerve cell Animals Benzhydryl Compounds Cold Temperature Dopamine Agents Dopamine Plasma Membrane Transport Proteins Female Hot Temperature Hypothermia Methamphetamine Mice Mice, Inbred C57BL Neostriatum Neurons Neuroprotective Agents Proto-Oncogene Proteins c-fos Tyrosine 3-Monooxygenase |
| spellingShingle |
Astroglia Dopamine Methamphetamine Modafinil Striatum Toxicity dopamine transporter glial fibrillary acidic protein methamphetamine modafinil placebo protein c fos tyrosine 3 monooxygenase benzhydryl derivative dopamine receptor stimulating agent methamphetamine modafinil neuroprotective agent animal cell animal experiment animal model animal tissue Article body temperature disorder body temperature measurement cell nucleus cellular distribution controlled study corpus striatum correlational study disease marker down regulation drug protein binding drug targeting environmental exposure environmental temperature female hyperthermia immunohistochemistry immunoreactivity mouse mouse model neuropharmacology neuroprotection neurotoxicity nonhuman priority journal protein determination protein expression protein localization thermal exposure thermoregulation tissue distribution upregulation animal C57BL mouse chemically induced cold cytology drug effects heat hypothermia metabolism neostriatum nerve cell Animals Benzhydryl Compounds Cold Temperature Dopamine Agents Dopamine Plasma Membrane Transport Proteins Female Hot Temperature Hypothermia Methamphetamine Mice Mice, Inbred C57BL Neostriatum Neurons Neuroprotective Agents Proto-Oncogene Proteins c-fos Tyrosine 3-Monooxygenase Differential Effects of Environment-Induced Changes in Body Temperature on Modafinil’s Actions Against Methamphetamine-Induced Striatal Toxicity in Mice |
| topic_facet |
Astroglia Dopamine Methamphetamine Modafinil Striatum Toxicity dopamine transporter glial fibrillary acidic protein methamphetamine modafinil placebo protein c fos tyrosine 3 monooxygenase benzhydryl derivative dopamine receptor stimulating agent methamphetamine modafinil neuroprotective agent animal cell animal experiment animal model animal tissue Article body temperature disorder body temperature measurement cell nucleus cellular distribution controlled study corpus striatum correlational study disease marker down regulation drug protein binding drug targeting environmental exposure environmental temperature female hyperthermia immunohistochemistry immunoreactivity mouse mouse model neuropharmacology neuroprotection neurotoxicity nonhuman priority journal protein determination protein expression protein localization thermal exposure thermoregulation tissue distribution upregulation animal C57BL mouse chemically induced cold cytology drug effects heat hypothermia metabolism neostriatum nerve cell Animals Benzhydryl Compounds Cold Temperature Dopamine Agents Dopamine Plasma Membrane Transport Proteins Female Hot Temperature Hypothermia Methamphetamine Mice Mice, Inbred C57BL Neostriatum Neurons Neuroprotective Agents Proto-Oncogene Proteins c-fos Tyrosine 3-Monooxygenase |
| description |
Methamphetamine (METH) exposure can produce hyperthermia that might lead to toxicity and death. Modafinil is a wake-promoting compound that is also been prescribed off-label to treat METH dependence. Modafinil has shown neuroprotective properties against METH harmful effects in animal models. The goal of the present study was to test if the prevention of hyperthermia might play a role on the neuroprotective actions of modafinil against METH toxicity using various ambient temperatures. METH was administered to female C57BL/6 mice in a binge regimen: 4 × 5 mg/kg, 2 h apart; modafinil (90 mg/kg) was injected twice, 1 h before first and fourth METH injections. Drugs were given at cold ambient temperature (14 °C) or hot ambient temperature (29 °C). Body temperature was measured during treatments. Brains were dissected out 6 days after treatments and processed for tyrosine hydroxylase (TH), dopamine transporter (DAT), GFAP and c-Fos immunohistochemistry. Exposure to hot ambient temperature exacerbated METH toxicity evidenced by striatal reductions in TH and DAT and increased GFAP immmunoreactivity. Modafinil counteracted reductions in TH and DAT, but failed to block astroglial activation. At both ambient temperatures tested modafinil did induce increments in GFAP, but the magnitude was significantly lower than the one induced by METH. Both drugs induced increases in c-Fos positive nuclei; modafinil did not block this effect. Our results suggest that protective effects of modafinil against METH-induced neurotoxicity may be dependent, in part, to its hypothermic effects. Nevertheless, modafinil maintained some protective properties on METH-induced alterations in the striatum at different ambient temperatures. © 2014, Springer Science+Business Media New York. |
| title |
Differential Effects of Environment-Induced Changes in Body Temperature on Modafinil’s Actions Against Methamphetamine-Induced Striatal Toxicity in Mice |
| title_short |
Differential Effects of Environment-Induced Changes in Body Temperature on Modafinil’s Actions Against Methamphetamine-Induced Striatal Toxicity in Mice |
| title_full |
Differential Effects of Environment-Induced Changes in Body Temperature on Modafinil’s Actions Against Methamphetamine-Induced Striatal Toxicity in Mice |
| title_fullStr |
Differential Effects of Environment-Induced Changes in Body Temperature on Modafinil’s Actions Against Methamphetamine-Induced Striatal Toxicity in Mice |
| title_full_unstemmed |
Differential Effects of Environment-Induced Changes in Body Temperature on Modafinil’s Actions Against Methamphetamine-Induced Striatal Toxicity in Mice |
| title_sort |
differential effects of environment-induced changes in body temperature on modafinil’s actions against methamphetamine-induced striatal toxicity in mice |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10298428_v27_n1_p71_Raineri http://hdl.handle.net/20.500.12110/paper_10298428_v27_n1_p71_Raineri |
| _version_ |
1768546759396556800 |