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Age differences in the sensitivity to clomipramine in an animal model of obsessive-compulsive disorder
A Fernández-Guasti1, R E Ulloa, H Nicolini
1Departamento de Farmacobiología, Centro de Investigación y Estudios Avanzados, Calz. De los Tenorios 235, Col. Granjas Coapa, 14330, México D.F., México. jfernand@mail.cinvestav.mx
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-HT(1A) 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-HT(1A) 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.