Beta-lactam antibiotic decreases acquisition of and motivation to respond for cocaine, but not sweet food, in C57Bl/6 mice

Abstract

No medication is approved to treat cocaine addiction, but mounting evidence suggests that glutamate-directed approaches may reduce cocaine dependence and relapse. We tested the hypotheses that the glutamate transporter subtype 1 activator, ceftriaxone, disrupts acquisition of cocaine self-administration, motivation to self-administer cocaine, and conditioned place preference in mice. Repeated ceftriaxone (200 mg/kg) reduced the ability of mice to acquire cocaine and the motivation to self-administer cocaine after successful acquisition without affecting acquisition of or motivation for sweet food. Repeated ceftriaxone had no effect on cocaine-conditioned place preference. These results suggest that a β-lactam antibiotic reduces the direct reinforcing strength of cocaine without producing nonspecific deficits in conditioned learning processes.

Figures

Fig. 1

The effect of CTX treatment on acquisition of cocaine (0.56 mg/kg/inf) (1A) or vanilla Ensure (50%) (1B) self-administration, and on motivation to self-administer cocaine (0.56 mg/kg/inf) (1C) or vanilla Ensure (50%) (1D). n=5-8/group; bars are S.E.M. * indicates significance from vehicle as determined by Bonferroni posttest.

Fig. 2

The effect of CTX treatment (200 mg/kg) on CPP induced by cocaine (COC) at 10 or 20 mg/kg (2A) and the effect of subsequent CTX treatment on re-expression as described in Methods (2B). n=9-12/group for test, 4-5/group for retest; bars are S.E.M.