Effects of ceftriaxone on conditioned nicotine reward in rats

Nicotine is the addictive compound in tobacco products which exerts psychosomatic effects that contribute to abuse and to low rates of abstinence in treatment-seeking smokers. At present, the most successful smoking cessation aide helps one in four individuals quit smoking at 1 year postcessation. New adjunctive therapies are needed to improve status of smoking-related public health crises, and β-lactam antibiotics are one class of potential therapies as they favorably augment extrasynaptic glutamate clearance. Our study used two-chamber place conditioning to assess effects of ceftriaxone (CTX) on persistence of conditioned nicotine reward. Rats were conditioned to associate nicotine (0.4 mg/kg, subcutaneous) with one context and vehicle with an alternative context. After initial post-test, rats received either daily ceftriaxone (200 mg/kg, intraperitoneal) or saline. All rats showed nicotine place preference during post-test 1. CTX-treated rats meeting extinction criterion by post-test 7 showed significantly reduced preference for the nicotine-paired context during post-test 2 compared with vehicle-treated rats. We interpret these data to support the further study of CTX as a smoking cessation aide. Our results suggest that CTX reduces persistence of conditioned nicotine reward and may be helpful for improving abstinence rates in a subset of treatment-seeking smokers.