Antidepressant-Like Effects of Ceftriaxone in Male C57BL/6J Mice

Background Excessive glutamatergic neurotransmission is hypothesized to be associated with depressive-like behaviors and possibly major depressive disorder (MDD). Recent evidence that β-lactam antibiotic agents stimulate uptake of glutamate suggests that this class of compounds might possess antidepressant-like activity. Methods Three-month old, male, C57BL/6J mice were administered ceftriaxone (200 mg/kg IP) for 14–18 days, then tested in the tail-suspension, forced swim, and novelty-suppressed feeding tests to determine whether ceftriaxone had similar effects to classical antidepressant compounds in these models. Results Ceftriaxone treatment had an antidepressant-like effect across models. Reduced immobility and decreased freezing were observed in the forced swim and tail suspension tests. The same trend was seen in novelty-suppressed feeding, but the effect was not statistically significant. Conclusion Ceftriaxone demonstrates antidepressant-like effects in several mouse models. This is consistent with the hypothesis that enhanced uptake of glutamate might have antidepressant-like effects.