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Age differences in the sensitivity to clomipramine in an animal model of obsessive-compulsive disorder

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Abstract

Rationale

Subtypes of obsessive-compulsive disorder (OCD) related to age could determine differential response to treatment.

Objectives

To explore possible age differences in the effect of clomipramine in an animal model of OCD.

Methods

The deficits on spontaneous alternation produced by 8-OH-DPAT and the preventing actions of clomipramine, desipramine and WAY 100635 were compared between young and adult rats.

Results

No age differences were found in spontaneous alternation. The 5-HT1A agonist, 8-OH-DPAT (0.031, 0.125, 0.5 and 2.0 mg/kg, −15 min) produced perseveration in young and adult rats. However, young rats were sensitive to a lower dose of 8-OH-DPAT. Clomipramine (10 mg/kg per three administrations) completely prevented the action of 8-OH-DPAT (0.5 mg/kg) in adult rats. However, this treatment as well as higher doses (15 mg/kg 3 administrations) or injected for longer periods (10 mg/kg 5 administrations) produced weak protective effects (versus 0.125 mg/kg 8-OH-DPAT) or had no action (versus 0.5 mg/kg 8-OH-DPAT) in young animals. WAY 100 635 (0.5 mg/kg) blocked the action of 8-OH-DPAT (0.5 mg/kg) in both young and adult rats. Desipramine (10 mg/kg/3 administrations) lacked of a preventive effect on the 8-OH-DPAT (0.5 mg/kg) action. This result indicated that the 5-HT1A receptor is involved in the deficits on spontaneous alternation produced by 8-OH-DPAT.

Conclusions

The present data shows important age differences in the effect of clomipramine in a model of OCD. Such differences could be relevant for the age variations in the response to treatment in clinical practice.

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Acknowledgements

The authors wish to thank Mr. Víctor Flores for animal care and technical assistance and Dr. Gabriela Rodríguez Manzo for language checking. R.E.U. received a doctorate fellowship from "Conacyt" number 119564.

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Authors and Affiliations

  1. Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados, Calz. De los Tenorios 235, Col. Granjas Coapa, 14330, México D.F., México

    A. Fernández-Guasti & R. E. Ulloa

  2. División de Investigaciones Clínicas, Instituto Nacional de Psiquiatría, México D.F., México

    H. Nicolini

  3. Hospital Psiquiátrico Infantil "Dr. Juan N. Navarro", , México D.F., México

    R. E. Ulloa

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  1. A. Fernández-Guasti
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  2. R. E. Ulloa
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  3. H. Nicolini
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Correspondence to A. Fernández-Guasti.

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Fernández-Guasti, A., Ulloa, R.E. & Nicolini, H. Age differences in the sensitivity to clomipramine in an animal model of obsessive-compulsive disorder. Psychopharmacology 166, 195–201 (2003). https://doi.org/10.1007/s00213-002-1301-1

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  • DOI: https://doi.org/10.1007/s00213-002-1301-1

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