Protective effects of sodium benzoate against toluene-induced reward enhancement, behavioral disturbances, and impaired synaptic plasticity in mice.

Toluene is one of the most commonly abused solvents. Inhibition of N-methyl-D-aspartate receptor (NMDAR) has been linked to the rewarding and behavioral effects of toluene. One of the avenues to enhance NMDAR function is to increase the levels of D-serine via inhibiting D-amino acids oxidase (DAAO) activity. The present study determined whether sodium benzoate, a DAAO inhibitor, could counteract the toluene-induced brain stimulation reward enhancement, behavioral disturbances, and hippocampal synaptic dysfunction after acute toluene exposure. Male mice received various doses of sodium benzoate before toluene exposure for assessment of intracranial self-stimulation (ICSS) thresholds, rotarod test, novel object recognition task, social interaction test, and long-term potentiation (LTP) and long-term depression (LTD) of hippocampal synaptic transmission. Sodium benzoate prevented the lowering of ICSS thresholds, motor incoordination, social withdrawal, object recognition memory deficit, and impaired LTP and LTD induced by toluene. These results indicate that sodium benzoate could ameliorate toluene-induced facilitation of brain reward function, behavioral disturbances, and synaptic plasticity impairment, suggesting that sodium benzoate may be a promising compound against acute toluene intoxication caused by unintentional or deliberate inhalation.