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

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Abstract

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.

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Acknowledgments

This work was taken in part from Paulina Soberanes’ B.Sc. dissertation. The authors wish to express their gratitude to Ms. María Isabel Beltrán, Mr. Abraham Contreras, and Isai Mendez for the animal care and technical assistance. The experimental procedures comply with the Mexican guidelines for the use and care of laboratory animals. This work was supported by grant 50636-M (to C.L.R) from Conacyt.

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  1. Nayeli Páez-Martinez

    Present address: Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Col. Sto. Tomás, México City, 11340, México

Authors and Affiliations

  1. Departamento de Farmacobiologia, Cinvestav, Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, Mexico City, C.P. 14330, Mexico

    Silvia L. Cruz, Paulina Soberanes-Chávez & Carolina López-Rubalcava

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  1. Silvia L. Cruz
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  2. Paulina Soberanes-Chávez
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  3. Nayeli Páez-Martinez
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Correspondence to Carolina López-Rubalcava.

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Cruz, S.L., Soberanes-Chávez, P., Páez-Martinez, N. et al. Toluene has antidepressant-like actions in two animal models used for the screening of antidepressant drugs. Psychopharmacology 204, 279–286 (2009). https://doi.org/10.1007/s00213-009-1462-2

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