Ceftriaxone upregulates the glutamate transporter in medial prefrontal cortex and blocks reinstatement of methamphetamine seeking in a condition place preference paradigm.

Autor: Abulseoud OA; Department of Psychiatry and Behavioral Science, University of Southern California, Los Angeles, CA, USA. Abulseoud.osama@mayo.edu, Miller JD, Wu J, Choi DS, Holschneider DP
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2012 May 25; Vol. 1456, pp. 14-21. Date of Electronic Publication: 2012 Mar 27.
DOI: 10.1016/j.brainres.2012.03.045
Abstrakt: Glutamate signaling plays an essential role in drug-seeking behavior. Using reinstatement of conditioned place preference (CPP), we determined whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of the glutamate transporter (EAAT₂) on glial cells, blocks methamphetamine-triggered reinstatement of CPP. Rats acquired methamphetamine CPP following 7 consecutive days of conditioning, during which each animal received pairings of alternating morning methamphetamine (2.5 mg/kg, IP) and afternoon saline (IP). Animals showing CPP were successfully extinguished with repeated twice daily saline administration over a 7-day period. Ceftriaxone (200 mg/kg, IP) was administered (vs. saline) once a day for 7 days during the extinction period. Upon successful extinction, animals received a single dose of methamphetamine (2.5 mg/kg, IP) for reinstatement and were tested for CPP one day later. Using real time PCR, EAAT₂ mRNA levels in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were quantified in response to ceftriaxone. Ceftriaxone blocked methamphetamine-triggered reinstatement of CPP and significantly increased EAAT₂ mRNA levels in the mPFC, with a trend towards significance in the NAc. In conclusion, Ceftriaxone modulated the expression of the glutamate transporter in a critical region of the cortico-striatal addiction circuitry and attenuated drug-seeking behavior in rats. Further research is needed to test the efficacy of compounds targeting the EAAT₂ in human methamphetamine-dependent users.
(Copyright © 2012 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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