Blockade of intracellular calcium release induces an antidepressant-like effect in the mouse forced swimming test.
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.
Galeotti
Nicoletta
N
Department of Preclinical and Clinical Pharmacology, University of Florence, Viale G. Pieraccini 6, I-50139 Florence, Italy. nicoletta.galeotti@unifi.it
Bartolini
Alessandro
A
Ghelardini
Carla
C
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001522:Behavior, Animal; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005707:Gallic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D046353:Immobility Response, Tonic / Q000187:drug effects; D007276:Injections, Intraventricular / Q000379:methods; D042541:Intracellular Space / Q000187:drug effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D045442:Rotarod Performance Test / Q000379:methods; D012433:Ryanodine / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D000928:Antidepressive Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D012433:Ryanodine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D002118:Calcium