Effect of subchronic lithium carbonate treatment on anxiolytic-like effect of citalopram and MKC-242 in conditioned fear stress in the rat.
We investigated the effect of citalopram [selective serotonin (5-HT) reuptake inhibitor] and MKC-242 (5-[3-¿(2S)-(1, 4-Benzodioxan-2-ylmethyl) amino¿propoxy]-1, 3-benzo-dioxol hydrochloride; a selective 5-HT(1A) receptor agonist) on the expression of conditioned freezing, an index of anxiety, following treatment with subchronic lithium carbonate (LiCO(3)). Male Sprague-Dawley rats were used in these experiments. Acute administration of citalopram (subcutaneously, s.c.) reduced freezing significantly at a high dose (30 mg/kg), while showing no effect at lower doses (3 and 10 mg/kg). Acute administration of MKC-242 (s.c.; 0.1-10 mg/kg) dose dependently reduced freezing. Subchronic LiCO(3) treatment (1 week; 0.05% or 0.2% LiCO(3) in diet; p.o.) showed no effect on freezing behavior. Acute treatment with both citalopram (3 and 30 mg/kg) and MKC-242 (1 mg/kg) after subchronic treatment with the higher, but not the lower concentration of LiCO(3) (1 week), reduced freezing markedly and significantly, as compared with either drug alone. These results suggest that subchronic LiCO(3) treatment enhanced the anxiolytic-like effects of these serotonergic drugs by facilitating central 5-HT neurotransmission at clinically therapeutic plasma lithium levels.
Muraki
I
I
Department of Psychiatry, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo, Japan. ihoko@med.hokudai.ac.jp
Inoue
T
T
Hashimoto
S
S
Izumi
T
T
Ito
K
K
Ohmori
T
T
Koyama
T
T
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D015283:Citalopram / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005239:Fear / Q000187:drug effects*; D016651:Lithium Carbonate / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000928:Antidepressive Agents; D015283:Citalopram; D004146:Dioxanes; D004149:Dioxoles; D016651:Lithium Carbonate; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C096294:osemozotan