β-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats.
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.
Rasmussen
Bruce A
BA
Department of Pharmaceutical Sciences, Temple University Health Sciences Center, 3307 North Broad Street, Philadelphia, PA 19140, USA.
Baron
David A
DA
Kim
Jae K
JK
Unterwald
Ellen M
EM
Rawls
Scott M
SM
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
D000900:Anti-Bacterial Agents; D027342:Excitatory Amino Acid Transporter 2; D007769:Lactams; D018698:Glutamic Acid; D002443:Ceftriaxone
Brain Res. 2000 Oct 13;880(1-2):224
11033012
Antimicrob Agents Chemother. 1995 Dec;39(12):2728-31
8593009
Amino Acids. 2006 May;30(3):307-9
16622598
Nat Rev Neurosci. 2009 Aug;10(8):561-72
19571793
J Neurosci. 2003 Aug 6;23(18):7176-82
12904478
Neuroscience. 2008 Apr 22;153(1):329-37
18353560
Behav Pharmacol. 2010 Mar;21(2):161-4
20215965
Stroke. 2007 Jan;38(1):177-82
17122424
J Neurosci. 2009 Jul 22;29(29):9239-43
19625514
Nature. 2005 Jan 6;433(7021):73-7
15635412
Neurology. 1996 Oct;47(4 Suppl 2):S19-25; discussion S26
8858047
J Antimicrob Chemother. 1984 Oct;14(4):427-30
6094424
J Neurosci. 2002 Oct 15;22(20):9134-41
12388621
Neuroscience. 2007 May 11;146(2):617-29
17363173
Drug Alcohol Depend. 2010 Mar 1;107(2-3):261-3
20004063
Antimicrob Agents Chemother. 1993 Jul;37(7):1518-24
8363385
Biol Psychiatry. 2010 Jan 1;67(1):81-4
19717140