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

Abstract

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. 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. 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. 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.