Ceftriaxone attenuates locomotor activity induced by acute and repeated cocaine exposure in mice

- β-Lactam antibiotic ceftriaxone attenuates development of cocaine-induced behavioral sensitization.
- β-Lactam antibiotic ceftriaxone counteracts pre-existing cocaine-induced behavioral sensitization.
- β-Lactam antibiotic ceftriaxone attenuates acute locomotor-activating effect of cocaine.
- β-Lactam compounds may be CNS-active therapeutics to treat cocaine abuse.

Ceftriaxone (CTX) decreases locomotor activation produced by initial cocaine exposure and attenuates development of behavioral sensitization produced by repeated cocaine exposure. An important question that has not yet been answered is whether or not CTX reduces behavioral sensitization to cocaine in cases in which the antibiotic is administered only during the period of cocaine absence that follows repeated cocaine exposure and precedes reintroduction to cocaine. We investigated this question using C57BL/6 mice. Mice pretreated with cocaine (15 mg/kg × 14 days) and then challenged with cocaine (15 mg/kg) after 30 days of cocaine absence displayed sensitization of locomotor activity. For combination experiments, CTX injected during the 30 days of cocaine absence attenuated behavioral sensitization produced by cocaine challenge. In the case in which CTX was injected together with cocaine for 14 days, development of behavioral sensitization to cocaine challenge was also reduced. CTX attenuated the increase in locomotor activity produced by acute cocaine exposure; however, its efficacy was dependent on the dose of cocaine as inhibition was detected against 30 mg/kg, but not 15 mg/kg, of cocaine. These results from mice indicate that CTX attenuates locomotor activity produced by acute and repeated cocaine exposure and counters cocaine's locomotor activating properties in a paradigm in which the antibiotic is injected during the period of forced cocaine absence that follows repeated cocaine exposure.