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.

Conflict of interest statement

Statement of Conflicts of Interest

The authors declare that they have no conflict of interest.

Figures

Fig. 1

Extracellular glutamate in the nucleus accumbens following repeated ceftriaxone (CTX) administration (50, 100, 200 mg/kg) or saline (SAL) (N = 7–9 rats per group). Two-way ANOVA revealed a significant drug effect [F (15, 176) = 6.608, P = 0.0026] and day effect [F (2, 56) = 18.97, P = 0.0002]. *P < 0.05 compared to saline-treated rats.

Fig. 2

Extracellular glutamate in the nucleus accumbens following local perfusion of ACSF by itself or ACSF containing DHK (1 μM) in rats previously treated with SAL or CTX (200 mg/kg) (N = 6 rats per group). Two-way ANOVA revealed a significant drug effect [F (3, 20) = 13.87, P < 0.0001]. *P < 0.05 compared to SAL + ACSF and +P < 0.05 compared to CTX + ACSF.