Glutamate transporter subtype 1 (GLT-1) activator ceftriaxone attenuates amphetamine-induced hyperactivity and behavioral sensitization in rats - PubMed (original) (raw)

Glutamate transporter subtype 1 (GLT-1) activator ceftriaxone attenuates amphetamine-induced hyperactivity and behavioral sensitization in rats

Bruce Rasmussen et al. Drug Alcohol Depend. 2011.

Abstract

Background: The β-lactam antibiotic and glutamate transporter subtype 1 (GLT-1) activator ceftriaxone prevents relapse to cocaine-seeking and inhibits morphine-induced physical dependence and tolerance in rats, but its efficacy against amphetamine-induced behaviors is unknown.

Methods: Here, we tested the hypothesis that ceftriaxone (200mg/kg, i.p.) inhibits hyperactivity produced by acute amphetamine administration (2mg/kg, i.p.) and sensitization of hyperactivity induced by repeated amphetamine exposure (2mg/kg, i.p.). For acute experiments, rats treated with ceftriaxone for 5 days were injected with amphetamine or saline on day 6.

Results: Amphetamine elicited less ambulatory and stereotypical activity in ceftriaxone-treated rats than in ceftriaxone-naïve rats. For chronic experiments, rats injected with ceftriaxone or saline for 8 days were also injected with amphetamine or saline on days 6-8 and then challenged with amphetamine 5 days later. Amphetamine produced greater ambulatory and stereotypical activity in amphetamine-pretreated rats than in rats previously naïve to amphetamine. Amphetamine challenge produced less ambulatory and stereotypical activity in rats pretreated with a combination of ceftriaxone (200mg/kg) and amphetamine than in rats pretreated with only amphetamine.

Conclusion: The present demonstration that ceftriaxone attenuates amphetamine-induced hyperactivity and behavioral sensitization suggests its documented efficacy against adverse cocaine and morphine effects extends to amphetamine.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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Figures

Fig. 1

Fig. 1

Effect of repeated ceftriaxone (CTX) (50, 100, 200 mg/kg) or saline (SAL) injections on the stereotypical (Panel A) or ambulatory (Panel B) response to an acute injection of amphetamine (AMPH) (2 mg/kg) or SAL. Data are expressed as mean stereotypical or ambulatory counts + S.E.M. quantified in 10-min bins. N = 8 rats/group except for the SAL + AMPH group (N=15). *p < 0.05, **p < 0.01, ***p < 0.001 compared to respective SAL + SAL group and +p < 0.05 compared to respective SAL + AMPH group.

Fig. 2

Fig. 2

Effect of repeated ceftriaxone (CTX) (200 mg/kg) or saline (SAL) injections on sensitization of stereotypical (Panel A) or ambulatory (Panel B) activity produced by repeated amphetamine (AMPH) (2 mg/kg) exposure. All rats were injected with AMPH on day 13 following pretreatment with SAL + SAL, CTX + SAL, SAL + AMPH, or CTX + AMPH. Data are expressed as mean stereotypical or ambulatory counts + S.E.M. quantified in 10-min bins. N = 8 rats/group. *p < 0.05, **p < 0.01, ***p < 0.001 compared to respective SAL + SAL pretreated group and +p < 0.05 compared to respective SAL + AMPH pretreated group.

Fig. 3

Fig. 3

Effect of an acute injection of ceftriaxone (CTX) (200 mg/kg) on the stereotypical (Panel A) or ambulatory (Panel B) response to an acute injection of amphetamine (AMPH) (2 mg/kg) or saline (SAL). Data are expressed as mean stereotypical or ambulatory counts + S.E.M. quantified in 10-min bins. N = 8 rats/group.

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