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

Psychopharmacology (Berl). 2003 Mar;166(3):195-201. doi: 10.1007/s00213-002-1301-1. Epub 2003 Feb 13.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Aging / psychology*
  • Animals
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Clomipramine / therapeutic use*
  • Desipramine / pharmacology
  • Dose-Response Relationship, Drug
  • Male
  • Obsessive-Compulsive Disorder / drug therapy*
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Antidepressive Agents, Tricyclic
  • Piperazines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Clomipramine
  • Desipramine