Perospirone, a novel antipsychotic drug, inhibits marble-burying behavior via 5-HT1A receptor in mice: implications for obsessive-compulsive disorder.
Perospirone is a novel atypical antipsychotic drug with dopamine (DA) D(2)- and serotonin (5-hydroxytryptamine, 5-HT) 5-HT(2A)-receptor antagonist, and 5-HT(1A)-receptor agonist properties. In the present study, we examined the effect of perospirone on marble-burying behavior, which has been considered an animal model of obsessive-compulsive disorder (OCD), compared with the effects of other antipsychotics such as haloperidol and risperidone. Perospirone at a dose of 10 mg/kg (p.o.) inhibited marble-burying behavior without affecting the locomotor activity in mice. On the other hand, haloperidol (0.1 mg/kg, i.p.) and risperidone (1 mg/kg, p.o.) showed significant suppression of locomotor activity at the dose that inhibited marble-burying behavior. Furthermore, the inhibition of marble-burying behavior by perospirone was antagonized by WAY100135 (10 mg/kg, i.p.), a selective 5-HT(1A)-receptor antagonist. WAY100135 at the same dose also antagonized the inhibition of marble-burying behavior by 8-OH-DPAT (3 mg/kg, i.p.), a selective 5-HT(1A)-receptor agonist. These findings suggest that perospirone may exhibit anti-OCD activity in clinical use and that 5-HT(1A)-receptor agonistic activity may be involved in the inhibition of marble-burying behavior by perospirone.
Matsushita
Michihiko
M
Department of Psychiatry, Fukuoka University School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Egashira
Nobuaki
N
Harada
Satoko
S
Okuno
Ryoko
R
Mishima
Kenichi
K
Iwasaki
Katsunori
K
Nishimura
Ryoji
R
Fujiwara
Michihiro
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy; D010879:Piperazines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
D014150:Antipsychotic Agents; D007211:Indoles; D054833:Isoindoles; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; D044282:Receptor, Serotonin, 5-HT1A; C081293:WAY 100135; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol; D018967:Risperidone; C065533:perospirone