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


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.
Cruz
Silvia L
SL
Departamento de Farmacobiologia, Cinvestav, Sede Sur, Calzada de Tenorios 235, Col. Granjas Coapa, Mexico City C.P. 14330, Mexico.
Soberanes-Chávez
Paulina
P
Páez-Martinez
Nayeli
N
López-Rubalcava
Carolina
C
D000818:Animals; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D002997:Clomipramine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D019417:Hindlimb Suspension / Q000523:psychology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology*; D013550:Swimming / Q000523:psychology; D014050:Toluene / Q000494:pharmacology*
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D018691:Excitatory Amino Acid Antagonists; D012997:Solvents; D014050:Toluene; D018698:Glutamic Acid; D007649:Ketamine; D016291:Dizocilpine Maleate; D002997:Clomipramine; D003891:Desipramine