TY - JOUR
T1 - Aripiprazole inhibits marble-burying behavior via 5-hydroxytryptamine (5-HT)1A receptor-independent mechanisms
AU - Egashira, Nobuaki
AU - Okuno, Ryoko
AU - Matsushita, Michihiko
AU - Abe, Moe
AU - Mishima, Kenichi
AU - Iwasaki, Katsunori
AU - Nishimura, Ryoji
AU - Oishi, Ryozo
AU - Fujiwara, Michihiro
PY - 2008/9/11
Y1 - 2008/9/11
N2 - Aripiprazole is a first next-generation atypical antipsychotic drug with dopamine system stabilizing, serotonin (5-hydroxytryptamine, 5-HT) 5-HT1A receptor partial agonistic, and 5-HT2A receptor antagonistic properties. In the present study, we examined the effect of aripiprazole on marble-burying behavior, which has been considered an animal model of obsessive-compulsive disorder, and compared this with the effects of other atypical antipsychotics such as olanzapine and quetiapine. Aripiprazole (1 mg/kg, i.p.) inhibited marble-burying behavior without affecting the locomotor activity in mice. Conversely, olanzapine (3 mg/kg, i.p.) and quetiapine (100 mg/kg, p.o.) showed significant suppression of locomotor activity and impairment of motor coordination at the dose that inhibited marble-burying behavior. On the other hand, a selective 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane (WAY100635, 3 mg/kg, i.p.) markedly antagonized the inhibition of marble-burying behavior by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 3 mg/kg, i.p.), a selective 5-HT1A/7 receptor agonist. By contrast, WAY100635 at the same dose had no effect on the inhibition of marble-burying behavior by aripiprazole (1 mg/kg, i.p.). Quinpirole, a dopamine D2 receptor agonist, showed significant suppression of locomotor activity at the dose that inhibited marble-burying behavior. Conversely, L-741,626, a selective dopamine D2 receptor antagonist, at a dose of 10 mg/kg inhibited marble-burying behavior without affecting the locomotor activity. On the other hand, ketanserin, a 5-HT2A receptor antagonist, had no effect on the marble-burying behavior. These findings suggest that aripiprazole may be a useful drug for the treatment of obsessive-compulsive disorder, and that aripiprazole inhibits the marble-burying behavior via 5-HT1A receptor-independent mechanisms.
AB - Aripiprazole is a first next-generation atypical antipsychotic drug with dopamine system stabilizing, serotonin (5-hydroxytryptamine, 5-HT) 5-HT1A receptor partial agonistic, and 5-HT2A receptor antagonistic properties. In the present study, we examined the effect of aripiprazole on marble-burying behavior, which has been considered an animal model of obsessive-compulsive disorder, and compared this with the effects of other atypical antipsychotics such as olanzapine and quetiapine. Aripiprazole (1 mg/kg, i.p.) inhibited marble-burying behavior without affecting the locomotor activity in mice. Conversely, olanzapine (3 mg/kg, i.p.) and quetiapine (100 mg/kg, p.o.) showed significant suppression of locomotor activity and impairment of motor coordination at the dose that inhibited marble-burying behavior. On the other hand, a selective 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane (WAY100635, 3 mg/kg, i.p.) markedly antagonized the inhibition of marble-burying behavior by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 3 mg/kg, i.p.), a selective 5-HT1A/7 receptor agonist. By contrast, WAY100635 at the same dose had no effect on the inhibition of marble-burying behavior by aripiprazole (1 mg/kg, i.p.). Quinpirole, a dopamine D2 receptor agonist, showed significant suppression of locomotor activity at the dose that inhibited marble-burying behavior. Conversely, L-741,626, a selective dopamine D2 receptor antagonist, at a dose of 10 mg/kg inhibited marble-burying behavior without affecting the locomotor activity. On the other hand, ketanserin, a 5-HT2A receptor antagonist, had no effect on the marble-burying behavior. These findings suggest that aripiprazole may be a useful drug for the treatment of obsessive-compulsive disorder, and that aripiprazole inhibits the marble-burying behavior via 5-HT1A receptor-independent mechanisms.
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U2 - 10.1016/j.ejphar.2008.06.100
DO - 10.1016/j.ejphar.2008.06.100
M3 - Article
C2 - 18644366
AN - SCOPUS:49749119128
VL - 592
SP - 103
EP - 108
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -