Blockade of intracellular calcium release induces an antidepressant-like effect in the mouse forced swimming test

Neuropharmacology. 2006 Mar;50(3):309-16. doi: 10.1016/j.neuropharm.2005.09.005. Epub 2005 Oct 24.


The role of intracellular calcium in the modulation of a depressant-like condition was investigated in the mouse forced swimming test. I.c.v. administration of TMB-8 (0.23-46.3 nmol per mouse), a blocker of Ca2+ release from intracellular stores, decreased the mouse immobility time. I.c.v. injection of thapsigargin (0.003-3 nmol per mouse), compound which selectively inhibits Ca2+ uptake into the endoplasmic reticulum, produced, 60 min after administration, a depressant-like condition. Xestospongin C (1-100 pmol per mouse i.c.v.), an InsP3-receptor antagonist, decreased the mouse immobility time. By contrast, d-myo-inositol (5.4-540 pmol per mouse i.c.v.), compound which produces InsP3, resulted in a depressant-like effect. Similarly, ryanodine (0.1-600 pmol per mouse i.c.v.), an RyR antagonist, decreased the immobility time values whereas the administration of 4-chloro-m-cresol (0.1-100 pmol per mouse i.c.v.), an RyR agonist, showed an opposite effect. The antidepressant-like effects observed with TMB-8, xestospongin C and ryanodine were comparable to that produced by the antidepressant drugs amitriptyline and clomipramine. The treatments employed did not produce any behavioural impairment of mice as revealed by the rota-rod and hole board tests indicating that the antidepressant- and depressant-like effects were not due to a compromised locomotor activity and spontaneous motility of the treated animals. These results indicate that a central variation in intracellular calcium contents is involved in the modulation of a depressive-like condition in the mouse forced swimming test. In particular, the blockade of both InsP3Rs and RyRs appears to play an important role in the induction of an antidepressant-like effect, whereas the stimulation of these receptors is involved in a depressant-like response of mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / pharmacology
  • Behavior, Animal
  • Calcium / metabolism*
  • Calcium Channel Blockers / administration & dosage
  • Depression / drug therapy
  • Depression / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Gallic Acid / administration & dosage
  • Gallic Acid / analogs & derivatives
  • Immobility Response, Tonic / drug effects
  • Injections, Intraventricular / methods
  • Intracellular Space / drug effects*
  • Male
  • Mice
  • Motor Activity / drug effects
  • Rotarod Performance Test / methods
  • Ryanodine / pharmacology
  • Swimming / psychology
  • Time Factors


  • Antidepressive Agents
  • Calcium Channel Blockers
  • Enzyme Inhibitors
  • Ryanodine
  • 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate
  • Gallic Acid
  • Calcium