Involvement of the sigma1 receptor in inhibiting activity of fluvoxamine on marble-burying behavior: comparison with paroxetine.
In the present study, we examined the involvement of the sigma1 receptor in the inhibitory effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine, compared with that of paroxetine, on marble-burying behavior, which is an animal model of obsessive-compulsive disorder. Sigma1 receptor agonists (+)-SKF 10047 and PRE-084 significantly inhibited marble-burying behavior. Sigma receptor antagonist BD 1047 and selective sigma1 receptor antagonist BD 1063 significantly attenuated the inhibition of marble-burying behavior by fluvoxamine. In contrast, selective sigma2 receptor antagonist SM-21 failed to affect the inhibition of marble-burying behavior by fluvoxamine. On the other hand, BD 1047 and BD 1063 had no effect on the inhibition of marble-burying behavior by paroxetine. These observations show that activation of the sigma1 receptor is a necessary component in the inhibitory effect of fluvoxamine on marble-burying behavior, and that the mechanism of its action is clearly different from that of paroxetine.
Egashira
Nobuaki
N
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka and Department of Pharmacy, Kyushu University Hospital, Fukuoka 812-8582, Japan. n-egashi@pharm.med.kyushu-u.ac.jp
Harada
Satoko
S
Okuno
Ryoko
R
Matsushita
Michihiko
M
Nishimura
Ryoji
R
Mishima
Kenichi
K
Iwasaki
Katsunori
K
Orito
Kensuke
K
Fujiwara
Michihiro
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000494:pharmacology; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D017374:Paroxetine / Q000494:pharmacology* / Q000627:therapeutic use; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology* / Q000627:therapeutic use; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014326:Tropanes / Q000494:pharmacology; D000097605:Sigma-1 Receptor
D002087:Butyrates; D005029:Ethylenediamines; D016666:Fluvoxamine; D009025:Morpholines; D017374:Paroxetine; D010620:Phenazocine; D010879:Piperazines; D011619:Psychotropic Drugs; D017480:Receptors, sigma; D017367:Selective Serotonin Reuptake Inhibitors; D014326:Tropanes; D000097605:Sigma-1 Receptor; C093337:1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine; C106107:sigma-2 receptor; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; C107044:SM 21; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; C012134:SK&F 10047