Age differences in the sensitivity to clomipramine in an animal model of obsessive-compulsive disorder.
BACKGROUND
Subtypes of obsessive-compulsive disorder (OCD) related to age could determine differential response to treatment.


OBJECTIVE
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.
Fernández-Guasti
A
A
Departamento 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
Ulloa
R E
RE
Nicolini
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000375:Aging / Q000523:psychology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D002997:Clomipramine / Q000627:therapeutic use*; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002997:Clomipramine; D003891:Desipramine