Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamine
Methamphetamine (METH) is one of the psychostimulants that is co-abused with ethanol. Repeated high doses of METH have been shown to cause increases in extracellular glutamate concentration. We have recently reported that ethanol exposure can also increase the extracellular glutamate concentration...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-09-01
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| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00427/full |
| _version_ | 1818016619746557952 |
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| author | Yusuf S Althobaiti Fahad S Alshehri Atiah H Almalki Youssef Sari Youssef Sari |
| author_facet | Yusuf S Althobaiti Fahad S Alshehri Atiah H Almalki Youssef Sari Youssef Sari |
| author_sort | Yusuf S Althobaiti |
| collection | DOAJ |
| description | Methamphetamine (METH) is one of the psychostimulants that is co-abused with ethanol. Repeated high doses of METH have been shown to cause increases in extracellular glutamate concentration. We have recently reported that ethanol exposure can also increase the extracellular glutamate concentration and downregulate glutamate transporter subtype 1 (GLT-1). GLT-1 is a glial transporter that regulates the majority of extracellular glutamate. A Wistar rat model of METH and ethanol co-abuse was used to examine the expression of GLT-1 as well as other glutamate transporters (xCT and GLAST). We also examined the body temperature in rats administered METH, ethanol or both drugs. We further investigated the effects of ceftriaxone (CEF), a β-lactam antibiotic known to upregulate GLT-1, in this METH/ethanol co-abuse rat model. After seven days of either ethanol (6 g/kg) or water oral gavage, Wistar rats received either saline or METH (10 mg/kg i.p. every 2 hrs x 4), followed by either saline or CEF (200 mg/kg) posttreatment. METH administered alone decreased GLT-1 expression in the NAc and PFC and increased body temperature, but did not reduce either xCT or GLAST expression in ethanol and water-pretreated rats. Interestingly, ethanol and METH were found to have an additive effect on the downregulation of GLT-1 expression in the NAc but not in the PFC. Moreover, ethanol alone caused GLT-1 downregulation in the NAc and elevated body temperature compared to control. Finally, CEF posttreatment significantly reversed METH-induced hyperthermia, restored GLT-1 expression, and increased xCT expression. These findings suggest the potential therapeutic role of CEF against METH- or ethanol/METH-induced hyperglutamatergic state and hyperthermia. |
| first_indexed | 2024-04-14T07:15:09Z |
| format | Article |
| id | doaj.art-c74bc600cfc0461f93fa6863c0853df4 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-14T07:15:09Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-c74bc600cfc0461f93fa6863c0853df42022-12-22T02:06:19ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2016-09-011010.3389/fnins.2016.00427211122Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamineYusuf S Althobaiti0Fahad S Alshehri1Atiah H Almalki2Youssef Sari3Youssef Sari4University of Toledo, College of Pharmacy and Pharmaceutical SciencesUniversity of Toledo, College of Pharmacy and Pharmaceutical SciencesUniversity of Toledo, College of Pharmacy and Pharmaceutical SciencesUniversity of Toledo, College of Pharmacy and Pharmaceutical SciencesUniversity of Toledo, College of Pharmacy and Pharmaceutical SciencesMethamphetamine (METH) is one of the psychostimulants that is co-abused with ethanol. Repeated high doses of METH have been shown to cause increases in extracellular glutamate concentration. We have recently reported that ethanol exposure can also increase the extracellular glutamate concentration and downregulate glutamate transporter subtype 1 (GLT-1). GLT-1 is a glial transporter that regulates the majority of extracellular glutamate. A Wistar rat model of METH and ethanol co-abuse was used to examine the expression of GLT-1 as well as other glutamate transporters (xCT and GLAST). We also examined the body temperature in rats administered METH, ethanol or both drugs. We further investigated the effects of ceftriaxone (CEF), a β-lactam antibiotic known to upregulate GLT-1, in this METH/ethanol co-abuse rat model. After seven days of either ethanol (6 g/kg) or water oral gavage, Wistar rats received either saline or METH (10 mg/kg i.p. every 2 hrs x 4), followed by either saline or CEF (200 mg/kg) posttreatment. METH administered alone decreased GLT-1 expression in the NAc and PFC and increased body temperature, but did not reduce either xCT or GLAST expression in ethanol and water-pretreated rats. Interestingly, ethanol and METH were found to have an additive effect on the downregulation of GLT-1 expression in the NAc but not in the PFC. Moreover, ethanol alone caused GLT-1 downregulation in the NAc and elevated body temperature compared to control. Finally, CEF posttreatment significantly reversed METH-induced hyperthermia, restored GLT-1 expression, and increased xCT expression. These findings suggest the potential therapeutic role of CEF against METH- or ethanol/METH-induced hyperglutamatergic state and hyperthermia.http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00427/fullMethamphetaminehyperthermiaGLASTGLT-1XCTethanol gavage |
| spellingShingle | Yusuf S Althobaiti Fahad S Alshehri Atiah H Almalki Youssef Sari Youssef Sari Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamine Frontiers in Neuroscience Methamphetamine hyperthermia GLAST GLT-1 XCT ethanol gavage |
| title | Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamine |
| title_full | Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamine |
| title_fullStr | Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamine |
| title_full_unstemmed | Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamine |
| title_short | Effects of ceftriaxone on glial glutamate transporters in Wistar rats administered sequential ethanol and methamphetamine |
| title_sort | effects of ceftriaxone on glial glutamate transporters in wistar rats administered sequential ethanol and methamphetamine |
| topic | Methamphetamine hyperthermia GLAST GLT-1 XCT ethanol gavage |
| url | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00427/full |
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