Toluene has antidepressant-like actions in two animal models used for the screening of antidepressant drugs

Rationale: Many abused solvents share a profile of effects with classical antidepressants. For example, toluene, which is a representative and widely abused solvent, has been reported to increase both serotonin and noradrenaline levels in several brain areas after an acute exposure and to act as a noncompetitive antagonist of the glutamatergic N-methyl-d-aspartic acid (NMDA) receptor subtype. Therefore, it is possible that toluene could possess antidepressant-like actions. Objective: To provide an initial screening of toluene's antidepressant-like actions in the forced swimming test (FST) and the tail suspension test (TST) in mice and to analyze its possible mechanism of action. Materials and methods: Two series of experiments were performed. In the first one, male animals were exposed to toluene (0, 500, 1,000, 2,000, or 4,000 ppm) in a static exposure chamber for 30 min, and immediately after, evaluated for antidepressant-like effects. The results were compared with those obtained from mice treated with the serotonergic antidepressant clomipramine (CMI), the noradrenergic antidepressant desipramine (DMI), and the glutamatergic antidepressants, ketamine and MK-801. In the second part, we analyzed the effect of a combined administration of a subeffective concentration of toluene with a suboptimal dose of the various antidepressants acting at different neurotransmitter systems. Results: Toluene produced a concentration-dependent antidepressant-like action in the FST and TST and facilitated both MK-801 and ketamine antidepressant-like effects, but not those of DMI or CMI. Conclusions: Toluene has antidepressant-like effects that are synergized with NMDA receptor antagonists.