title: Effects of repeated high-dose methamphetamine and ceftriaxone post-treatments on tissue content of dopamine and serotonin as well as glutamate and glutamine.
abstract: Repeated exposure to high doses of methamphetamine (METH) is known to alter several neurotransmitters in certain brain regions. Little is known about the effects of ceftriaxone (CEF), a β-lactam antibiotic, known to upregulate glutamate transporter subtype 1, post-treatment on METH-induced depletion of dopamine and serotonin (5-HT) tissue content in brain reward regions. Moreover, the effects of METH and CEF post-treatment on glutamate and glutamine tissue content are not well understood. In this study, Wistar rats were used to investigate the effects of METH and CEF post-treatment on tissue content of dopamine/5-HT and glutamate/glutamine in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Rats received either saline or METH (10mg/kg, i.p. every 2h×4) followed by either saline or CEF (200mg/kg, i.p, every day×3) post-treatment. METH induced a significant depletion of dopamine and 5-HT in the NAc and PFC. Importantly, dopamine tissue content was completely restored in the NAc following CEF post-treatment. Additionally, METH caused a significant decrease in glutamate and glutamine tissue content in PFC, and this effect was attenuated by CEF post-treatment. These findings demonstrate for the first time the attenuating effects of CEF post-treatment on METH induced alterations in the tissue contents of dopamine, glutamate, and glutamine.
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH, United States.
authors.forename: Yusuf S
authors.initials: YS
authors.lastname: Althobaiti
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH, United States; University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Medicinal and Biological Chemistry, Toledo, OH, United States.
authors.forename: Atiah H
authors.initials: AH
authors.lastname: Almalki
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH, United States; University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Medicinal and Biological Chemistry, Toledo, OH, United States.
authors.forename: Sujan C
authors.initials: SC
authors.lastname: Das
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH, United States.
authors.forename: Fahad S
authors.initials: FS
authors.lastname: Alshehri
authors.affiliation: University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology and Experimental Therapeutics, Toledo, OH, United States; University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Medicinal and Biological Chemistry, Toledo, OH, United States. Electronic address: youssef.sari@utoledo.edu.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Sari
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000697:Central Nervous System Stimulants; D005973:Glutamine; D012701:Serotonin; D018698:Glutamic Acid; D008694:Methamphetamine; D002443:Ceftriaxone; D004298:Dopamine
keywords: Ceftriaxone; Dopamine; Glutamate; Glutamine; Methamphetamine; Serotonin