Establishment of a mouse model to assess brain neurotransmitter level and learning performance simultaneously following toxic chemical exposure: using in vivo microdialysis and schedule-controlled operant behavior.

Most of the volatile organic compounds used in industrial and household products are reported to be toxic. While the effects of toxic chemicals on pulmonary and other systemic functions have been studied substantially, little is known about their effects on higher brain functions, particularly on the events in learning performance. From the particular perspective of environmental health, it is necessary to examine the toxic effects of environmental chemicals on higher brain functions. The aim of the present study is to establish a mouse model for simultaneous assessment of the effect of toluene (150 mg/kg, i.p.) on extracellular glutamate level in the hippocampus, using in vivo microdialysis and learning performance with a procedure of schedule-controlled operant behavior (SCOB). Different patterns of hippocampal glutamate level were observed in control and toluene-treated mice during learning performance. During learning performance in an operant chamber, control mice showed a saturated and persistent increased glutamate level with good learning performance, while toluene-treated mice showed a decreased glutamate level with poor learning performance. This is the first time to establish a new method to assess the effect of environmental chemical exposure on the brain neurotransmitter level during learning performance in an animal model.