title: β-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats.
abstract: We investigated the short- and long-term effects of ceftriaxone on glutamate transporter subtype 1 (GLT-1) transporter activity and extracellular glutamate in the rat nucleus accumbens. Repeated ceftriaxone administration (50, 100 or 200 mg/kg, i.p.) produced a dose-dependent reduction in glutamate levels that persisted for 20 days following discontinuation of drug exposure. The ceftriaxone effect was prevented by the GLT-1 transporter inhibitor dihydrokainate (1 μM, intra-accumbal). These results suggest that β-lactam antibiotics produce an enduring reduction in glutamatergic transmission in the brain reward center.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University Health Sciences Center, 3307 North Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Rasmussen
authors.forename: David A
authors.initials: DA
authors.lastname: Baron
authors.forename: Jae K
authors.initials: JK
authors.lastname: Kim
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Unterwald
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D007769:Lactams / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013995:Time
chemical_list: D000900:Anti-Bacterial Agents; D027342:Excitatory Amino Acid Transporter 2; D007769:Lactams; D018698:Glutamic Acid; D002443:Ceftriaxone
references.citation: Brain Res. 2000 Oct 13;880(1-2):224
references.pmid: 11033012
references.citation: Antimicrob Agents Chemother. 1995 Dec;39(12):2728-31
references.pmid: 8593009
references.citation: Amino Acids. 2006 May;30(3):307-9
references.pmid: 16622598
references.citation: Nat Rev Neurosci. 2009 Aug;10(8):561-72
references.pmid: 19571793
references.citation: J Neurosci. 2003 Aug 6;23(18):7176-82
references.pmid: 12904478
references.citation: Neuroscience. 2008 Apr 22;153(1):329-37
references.pmid: 18353560
references.citation: Behav Pharmacol. 2010 Mar;21(2):161-4
references.pmid: 20215965
references.citation: Stroke. 2007 Jan;38(1):177-82
references.pmid: 17122424
references.citation: J Neurosci. 2009 Jul 22;29(29):9239-43
references.pmid: 19625514
references.citation: Nature. 2005 Jan 6;433(7021):73-7
references.pmid: 15635412
references.citation: Neurology. 1996 Oct;47(4 Suppl 2):S19-25; discussion S26
references.pmid: 8858047
references.citation: J Antimicrob Chemother. 1984 Oct;14(4):427-30
references.pmid: 6094424
references.citation: J Neurosci. 2002 Oct 15;22(20):9134-41
references.pmid: 12388621
references.citation: Neuroscience. 2007 May 11;146(2):617-29
references.pmid: 17363173
references.citation: Drug Alcohol Depend. 2010 Mar 1;107(2-3):261-3
references.pmid: 20004063
references.citation: Antimicrob Agents Chemother. 1993 Jul;37(7):1518-24
references.pmid: 8363385
references.citation: Biol Psychiatry. 2010 Jan 1;67(1):81-4
references.pmid: 19717140